# Anti-MAP Therapy Support Group



## Crohn2357

The Anti-MAP Therapy Support Group.


* Some papers on the immunodeficiency hypothesis*

Crohn's as an immune deficiency: from apparent paradox to evolving paradigm.
https://www.ncbi.nlm.nih.gov/pubmed/23256761

Disordered macrophage cytokine secretion underlies impaired acute inflammation and bacterial clearance in Crohn's disease
http://jem.rupress.org/content/206/9/1883.full

Revisiting Crohn's disease as a primary immunodeficiency of macrophages
http://jem.rupress.org/content/206/9/1839.full

Is Crohn’s disease due to defective immunity?
http://gut.bmj.com/content/56/1/2?i...7f2e2a3173ce65be17d31bd0&keytype2=tf_ipsecsha

Defective acute inflammation in Crohn's disease: a clinical investigation
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(06)68265-2/fulltext

Neutrophil Dysfunction In Crohn's Disease
http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(76)91024-2/abstract

Vitamin D, NOD2, autophagy and Crohn’s disease
http://www.tandfonline.com/doi/full/10.1586/eci.10.31

Abnormalities in the handling of intracellular bacteria in Crohn's disease: a link between infectious etiology and host genetic susceptibility.
https://link.springer.com/article/10.1007/s00005-008-0026-1

Crohn’s disease as an immunodeficiency
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4618314/

Defective innate immunity in inflammatory bowel disease: a Crohn's disease exclusivity?
https://insights.ovid.com/pubmed?pmid=21483259

Is Crohn's disease an immunodeficiency? A hypothesis suggesting possible early events in the pathogenesis of Crohn's disease.
https://www.ncbi.nlm.nih.gov/pubmed/10877227

Crohn's disease: an immune deficiency state.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4568313/

Integrating theories of the etiology of Crohn's disease. On the etiology of Crohn's disease: questioning the hypotheses.
https://www.medscimonit.com/download/index/idArt/445257

The immunopathogenesis of Crohn’s disease: a three-stage model
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4529487/

Mycobacteria in Crohn's disease: A persistent hypothesis
https://insights.ovid.com/pubmed?pmid=17012971

Mycobacteria in Crohn’s disease: how innate immune deficiency may result in chronic inflammation
http://www.tandfonline.com/doi/abs/10.1586/eci.10.29?journalCode=ierm20

...

*Compiled literature and resources on the MAP hypothesis
*
http://www.crohnsmapvaccine.com/downloads/ 

http://www.crohnsmapvaccine.com/map-papers/

https://humanpara.org/crohns-resources-page/

https://humanpara.org/core-research-pack/

https://docs.google.com/viewerng/vi...7/02/CD-Core-Research-Pack-10-16.pdf&hl=en_US

http://humanpara.org/news/ 


*RHB-104*

http://www.redhillbio.com/rhb-104

Efficacy and Safety of Anti-MAP Therapy in Adult Crohn’s Disease (MAPUS).

Open Label Efficacy and Safety of Anti-MAP (Mycobacterium avium spp. paratuberculosis) Therapy in Adult Crohn’s Disease (MAPUS2).

RedHill Biopharma Accelerates RHB-104 Phase III Study in Crohn’s Disease with Top-Line Results Expected Mid-2018


*Crohn's Map Vaccine*

http://www.crohnsmapvaccine.com

https://www.facebook.com/crohnsmapvaccine

https://www.youtube.com/channel/UCUJ_Xij68Jl0dqArtlfYBcw/videos

A Study to Determine the Safety and Immunogenicity of a Candidate MAP Vaccine ChAdOx2 HAV in Healthy Adult Volunteers

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2017 MAP Conference Presentations

The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference 2017

Anti MAP Forums and Groups

Human Paratuberculosis Foundation Facebook Group

Testimonials

Patient Stories

Patient Information Leaflet: Anti-MAP antibiotic therapy for the treatment of Crohn’s Disease

Treatment of Crohn’s Disease using Anti-MAP (AMAT) Therapy

AMAT questions answered by Dr. William M. Chamberlin

MAP Specialists

MAP Doctors and Research Centers Around the Globe

MAP diagnostic test by Otakaro Pathways

https://www.anti-map.org


*Videos on Youtube
*
Crohn's: autoimmune or infectious disease? Public presentation by Marcel Behr.

Prof Borody; Crohn's Interview - Part 1 of 9

Part 1-CROHN M.A.P. by John Hermon Taylor

Patients' stories


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## Deleted member 431298

great initiative 
+1


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## irishgal

Love it!


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## Bufford

Interesting, and perhaps a glimmer of hope.


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## Crohn2357

Macrolides and other antibiotics may cause serious neurological and psychiatric side effects in some people.




> The mechanisms involved in macrolide induced psychiatric reactions
> are not well established. Several theories have been proposed:
> 1) drug interactions due to the inhibition of cytochrome
> P450 by clarithromycin; 2) accumulation of the active metabolite
> 14-OH of clarithromycin in the central nervous system; 3)
> increased levels of blood cortisol and prostaglandins, hormones
> that are associated with mania (6,10,11).


Psychiatric adverse reaction induced by Clarithromycin
http://www.eurannallergyimm.com/con...eaction-induced-clarithromycin-118allasp1.pdf



> Pharmacovigilance data collected from several European countries show that macrolides can provoke neuropsychological adverse effects such as hallucinations, delirium, manic episodes and sometimes depression, in both adults and children. These effects seem to be rare and are reversible on macrolide withdrawal.


Neuropsychological effects of macrolides
http://english.prescrire.org/en/F87B2B090D3CB6CFFE0D2FF7DDD42318/Download.aspx



> In the literature, different forms of clinical
> symptoms have been described as consequences
> of the effect of macrolide antibiotics on the CNS
> (mania, psychotic reaction, delirium, nightmares,
> psychomotor agitation)6-11. In 1981, Cohen and
> Weitz first described two cases of psychiatric
> complications in patients who received
> erythromycin12. The exact mechanism of the
> described side effects is not known. There are
> numerous assumptions and explanations that the
> active metabolite of erythromycin passes through
> the blood-brain barrier and causes imbalance
> between GABA-ergic and glutamatergic activities
> in favor of the latter13. The literature also mentions
> the possible antagonization of GABA A receptors,
> protein and pyridoxine synthesis inhibition14, and
> an increase in endogenous glucocorticoids in the
> CNS15. Thus, in the face of various assumptions,
> the mechanism remains unknown. We must bear
> in mind that erythromycin is one of the important
> inhibitors of cytochromal enzymes in the liver,
> possibly also affecting the pharmacokinetics of
> other drugs in the body.


Erythromycin-Induced Psychotic Decompensation in a
Patient Affected by Paranoid Schizophrenic Psychosis 
http://www.tandfonline.com/doi/pdf/10.5455/bcp.20140802124414



> The principal side effects of clarithromycin are gastrointestinal; however, less commonly, CNS side effects have been reported, including dizziness, vertigo, anxiety, insomnia, tinnitus, confusion, disorientation, hallucinations, psychosis, and depersonalisation.1 At the time of writing the Committee on Safety of Medicines (CSM)/Medicines Control Agency (MCA) have received 219 reports of suspected clarithromycin induced psychiatric disorders including psychosis (n=5), depersonalisation (n=5), and suicidal ideation (n=4) (CSM, personal communication). It has been postulated that macrolide antibiotics may cause a psychosis-like syndrome via their inhibitory action on glutamatergic neurotransmission in the brain.2 Nevirapine has not been reported to cause serious CNS adverse effects.3


Neuropsychiatric reaction induced by clarithromycin in a patient on highly active antiretroviral therapy (HAART)
http://sti.bmj.com/content/77/4/297



> We reported two cases of end-stage renal disease (ESRD) patients who developed hallucinations such as vivid images of worms after taking clarithromycin. Similar to previous case reports of clarithromycin neurotoxicity, the visual hallucination resolved upon cessation of clarithromycin.


Clinical manifestation of macrolide antibiotic toxicity in CKD and dialysis patients 
https://academic.oup.com/ckj/article/7/6/507/2918797/Clinical-manifestation-of-macrolide-antibiotic



> Although the psychotropic effects of antibiotics are not commonly utilized therapeutically, the commonly associated side effects confirm their potential to influence CNS function. Several antibiotic medications have been known to cause confusion, anxiety and depression and in some instances, psychosis [13]. Although unfavorable in a therapeutic context, these effects are often influenced by age, dosage, blood–brain barrier (BBB) permeability and drug interactions. Research into the mechanisms behind these effects may help to elucidate a therapeutic application. Penicillin for example was known to act on GABA receptors, a mechanism thought to be responsible for many of the side effects [14]. Other classes of antimicrobial compounds, particularly the antimalaria treatment methylene blue and several antituberculosis drugs, have been shown to have monoamine oxidase (MAO) inhibitor (MAOI) properties.


Psychotropic effects of antimicrobials and immune modulation by psychotropics: implications for neuroimmune disorders
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3494283/

Nervous System Effects of Antituberculosis Therapy
https://link.springer.com/article/10.2165/11534340-000000000-00000

Adverse effects of macrolide antibacterials.
https://www.ncbi.nlm.nih.gov/pubmed/8280403

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections†
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2952976/

Nervous system effects of antituberculosis therapy.
https://www.ncbi.nlm.nih.gov/pubmed/20658798/

Neurological manifestations and toxicities of the antituberculosis drugs. A review.
https://www.ncbi.nlm.nih.gov/pubmed/20658798/

[Adverse effects of antitubercular drugs: epidemiology, mechanisms, and patient management].
https://www.ncbi.nlm.nih.gov/pubmed/17336011

Adverse Effects of Macrolide Antibacterials
https://link.springer.com/article/10.2165/00002018-199309050-00004?no-access=true


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## Crohn2357

Other possible side effects that I remember:

Fatigue, nausea, headaches, bad taste in mouth, dizziness, brain fog, reduced apetite, diarrhea, joint pain, oral candidiasis, c. diff. infection, cardiac arrythmia and hepatoxicity, tendon rupture (Cipro), bacterial resistance to antibiotics.


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## Deleted member 431298

Another anecdotal case report of long-term remission induced by anti-MAP treatment.

Summary:
Dr. Lipton struggled with IBD from 1986 until 2004. She had multiple flares, sometimes called Ulcerative Colitis, but finally Crohn’s. One day, as she was resting in bed recovering from a flare that landed her in the hospital, she read a medical magazine and came across an article about a microbial agent, Mycobacterium Avium Paratuberculosis (MAP), and its potential connection to Crohn’s disease in humans. 
On 12/10/04 Dr. Lipton began a special antibiotics regimen guided by Dr. Borody. She responded to the treatment well, all her Crohn’s symptoms vanished. She spent 5 years on the antibiotics, ensuring that all the harmful MAP bacteria were eradicated. She decided to stop the antibiotics treatment in 2010, feeling that this allowed plenty of time to assure her sustained wellness. These days, Dr. Lipton continues to be in complete and total remission, without any special diet and without any maintenance medications.


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## Crohn2357

OleJ said:


> Another anecdotal case report of long-term remission induced by anti-MAP treatment.
> 
> Summary:
> Dr. Lipton struggled with IBD from 1986 until 2004. She had multiple flares, sometimes called Ulcerative Colitis, but finally Crohn’s. One day, as she was resting in bed recovering from a flare that landed her in the hospital, she read a medical magazine and came across an article about a microbial agent, Mycobacterium Avium Paratuberculosis (MAP), and its potential connection to Crohn’s disease in humans.
> On 12/10/04 Dr. Lipton began a special antibiotics regimen guided by Dr. Borody. She responded to the treatment well, all her Crohn’s symptoms vanished. She spent 5 years on the antibiotics, ensuring that all the harmful MAP bacteria were eradicated. She decided to stop the antibiotics treatment in 2010, feeling that this allowed plenty of time to assure her sustained wellness. These days, Dr. Lipton continues to be in complete and total remission, without any special diet and without any maintenance medications.


An earlier post from Dr. Lipton:

https://www.psychologytoday.com/blog/pura-vida/201402/treating-crohns-disease

The comments section has some information too.


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## Deleted member 431298

Recently uploaded to YouTube:  
a five minutes long profile of Dr. Thomas Borody, who is one of the practitioners administering Anti-MAP therapy from his clinic in Sydney, Australia.
He is one of the few doctors to openly state that he firmly believes CD to be an infectious disease. 
Dr. Borody was also behind the development of the triple antibiotics therapy for gastric ulcers, which target the underlying infection by the H. Pylori bacteria. 
The treatment is now considered the gold standard for gastric ulcers.

PS. Thank you! Crohn2357 for posting the link to Dr. Lipton's blog page. You are right, both the blog and the comments are an interesting read!


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## Guerrero

Hi guys, have you been donating for the anti-map vaccine? 

have you been on some anti map therapy?


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## Deleted member 431298

Hi Guerrero.
No, to be honest I have not yet donated to the vaccine development. I know I ought to. I did support John Aitken's lab by ordering a MAP blood culture test.
Did you donate?
Also, I have not tried anti-MAP therapy. I am monitoring the news from Redhill about their phase III study, and I am in an almost daily debate with myself whether I should try to find a GI that will prescribe the drugs or not. It's just that no doctor I have ever spoke to seems to think MAP could be causing CD. Also, none have shown real interest in the research. So I would probably have to look abroad (to the UK) and that is just a bit of a mouthful to do.

It would be very interesting to hear from someone currently on the antibiotics!


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## irishgal

Ole - I'm on AMAT and it has changed my life. The antibiotics do work for some people. I have inflammatory markers and colonoscopy results from before and after AMAT. Horrible before, felt like I was pretty close to being hospitalized and barely able to leave my house, to no trace of Crohn's even three years later. The docs call me a miracle responder. After 25 years of this horrible disease, it's like I never had it. My mucosa is healed, and I feel great. Never thought it would happen. So at least for some people, it works. Sometimes it's not as dramatic, but a fair amount reach remission. At least as good as other therapies in my opinion.


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## irishgal

Also Ole - have you seen HumanPara.org? There are other patient stories on there and since I talked to the people and put their stories on the site myself, I know for sure these are real people who have had their life changed by AMAT. It's interesting to see the variety of response to AMAT. Some were quick like me, others took a longer time. I know for some, it doesn't work or they cna't tolerate the meds. Look under the Crohn's tab. I also think RedHill will be very successful. Just waiting for the final data. We're getting close!


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## Deleted member 431298

Thanks, Irisgal for the useful and relevant info. Congratulations with being in complete remission without any of the usual heavy immunosuppresant drugs. That is truly amazing.

I have been in remission on Methotrexate, and five month ago I sent blood to John Aitken's lab and they found viable MAP in my blood. Very low numbers, though, consistent with a patient in remission (which I was at the time). As an experiment, I have tried to quit dairy/beef and taper the MTX.. could it be that avoiding re-exposure to MAP alone would keep me in remission?
Sadly the answer seems to be no. Six weeks without MTX now and the CD symptoms have returned over the last two weeks.
I will now send another blood sample to Aitken, to see if more viable MAP can be found. I hope that can assist the decition whether to try to get on AMAP or not.

Although I have been visiting humanpara.org alot, I had not noticed the patient stories. I am going to read through them with interest. 
Cheers.


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## irishgal

Sorry you are flaring Ole. I think it's a lot more than MAP ingestion once the disease triggers. It's trying to control the whole immune cascade. Will be interesting wha your current sample will show as compared to the last one. And I definitely tried all of the conventoinal therapies first (minues 6MP and MTX) but nothing worked. AMAT wasn't so much of a choice as it was the only viable thing left! But I'm glad I did it. Trying to figure out an end game as I've been on for 3 years now. Let me know how you do!


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## Deleted member 431298

Thanks, will do .
_Trying to figure out an end game as I've been on for 3 years now._
I take it you already studied Dr. Lipton's case? An article about her reads:
_She spent 5 years on the antibiotics, ensuring that all the harmful MAP bacteria were eradicated (this kind of bacteria is a very slow propagator, so the working assumption is that it takes a long time to ensure all traces are eliminated). She decided to stop the antibiotics treatment in 2010, feeling that this allowed plenty of time to assure her sustained wellness._

http://gutharmony.net/index.php/2017/10/01/seem-cured-crohns-disease/


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## irishgal

Yes - I've spoken with Dr. Lipton, but I think back then the thought was that you could erradicate it completely. In my long term case, I don't think that's going to be possible, and I'll still be genetically susceptible. My goal is to keep the little I have left in dormancy.


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## Deleted member 431298

Update on my getting-to-know-my-MAP-levels-trend quest:

I Fedex'ed two blood samples yesterday. Quite the logistic puzzle, but I'll spare you the details. I emailed the lab, briefly explaining my situation: That I had another test done five month back, positive but with low numbers of MAP (I was in remission at the time). Then, how I had tapered Methotrexate and stopped altogether two month ago, and was now in a (mild) flare. 
John Aitken himself replied, and took the time to explain a few things (I am really impressed he did):

He said they see a gradual reduction of plasma levels of MAP in the first six month after AMAT treatment is started, but that it takes alot longer to clear the organisms inside the macrophages. 
He also explained that it is the extracellular MAP that cause inflammation, by producing biofilm. Biofilm production is hindered inside the cells. Anti-MAP therapies, he said, reach the extracellular bacteria first because are an easy target. The drugs prevent them from forming biofilm, thus giving a theraptutic effect. The intercellular ones are harder to get.
It seems no matter how long MAP is targeted by antibiotics, some mycobacteria manage to survive. So basically for the last bit he echoes what you write, Irishgirl, that the goal (at the moment) must be to limit the infection to a point where the mycobacteria can not form biofilm (dormancy).

What a bummer that appearently AMAT is not able to clear the MAP infection completely. 
Maybe then the Crohns MAP Vaccine is our best bet in the long run, and the antibiotics to be seen as a bridge therapy until JHT and his team hopefully completes stage III with success.

Irishgirl - if AMAT is no longer an option, what other options are you considering?  
Could a low dose MTX maybe work? I seem to be in remission on 7.5 - 10 mg / week. Then again- the reason I investigate this is I really want to get off MTX, because of the side effects (nausea, anemia, cancer risk).
Or why not just stay on AMAT? Are you experiencing side effects?

By the way, your story, and the patient stories at HumanPara are really encouraging. I understand you have been a part of making human para, congratulations on a job well done.


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## Crohn2357

OleJ said:


> Traditional therapies, he said, reach the extracellular bacteria which are an easy target. The drugs prevent them from forming biofilm, thus giving a theraptutic effect.


What do you mean by "traditional therapies" and "the drugs"?

I've used mtx injections three years ago. It's a nasty drug; but if it keeps you in remission with a dosage of 7.5 - 10 mg/week, then I think it is not a bad deal. It can save you some time until the Redhill study publishes its results.


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## Crohn2357

Cytotoxicity of macrolide antibiotics


Influence on Mitochondria and Cytotoxicity of Different Antibiotics Administered in High Concentrations on Primary Human Osteoblasts and Cell Lines▿
http://aac.asm.org/content/51/1/54.full

Cytotoxicity of macrolide antibiotics in a cultured human liver cell line.
https://www.ncbi.nlm.nih.gov/pubmed/8889721

Macrolide Antibiotics Exhibit Cytotoxic Effect under Amino Acid-Depleted Culture Condition by Blocking Autophagy Flux in Head and Neck Squamous Cell Carcinoma Cell Lines
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0164529

Mechanisms of Action and Clinical Application of Macrolides as Immunomodulatory Medications
http://cmr.asm.org/content/23/3/590.full


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## Deleted member 431298

Crohn2357 said:


> A) What do you mean by "traditional therapies" and "the drugs"?
> 
> B) I've used mtx injections three years ago. It's a nasty drug; but if it keeps you in remission with a dosage of 7.5 - 10 mg/week, then I think it is not a bad deal. It can save you some time until the Redhill study publishes its results.


ad A). both should have referred to anti-MAP therapy. I corrected it in the post.
ad B). my thinking too. I try to look to the next therapy, though, because I have learned the hard way immunosuppressants can fail. I had a really bad kidney infection, likely from anti-TNFa drugs. Those drugs being the only thing doctors suggest, AMAT is probably the only option left for med if MTX fails to work or if I get another opportunistic infection.
What drug(s) are you currently taking, if I may ask?

Re. your links to cytotoxicity of macrolides, can you explain a little more about what that means: what happens if one gets such a reaction, what are the symptoms, and will it reverse if you quit the drugs?

Do you know if rifabutin and clofazimine are also considered macrolides, or it it only clarithomyzin?

Also, do you know if such reactions have been reported with AMAT therapy (such as in the Selby study)?


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## irishgal

OleJ - I've been on AMAT full strength for nearly 3 years, and started getting a slight bit of joint pain which I couldn't determine if it was from the antibiotics or if it was the CD breaking through. My version of CD seems to break through therapies quickly (Remi only made it 6 months) and I ran out of anything approved, so went to AMAT. I was lucky thta stopped it cold, but I'm under no illusion that eventually the disease will figure a way around even AMAT. The only way to puzzle out the joint pain was to stop AMAT - a scary prospect after 3 years of being better!

I talked to my docs, and they all thought it was safe to pulse one week on, one off. Last week I stopped the antibiotics completely, promptly caught my husband's upper respiratory infection, and was miserable all week, but no GI pain, no CD symptoms, and the joint pain almost entirely went away. So it looks to be the meds giving me joint issues, and I wonder if that will continue with the every other week system. I had both CD caused joint pain prior to AMAT, and also bad joint issues when I was on levofloxicin as part of AMAT. I dropped the levo, and am only on clarithro and rifampin now, plus low dose naltrexone. I also daded some supplements, including a spore forming probiotic called MegaSporeBiotic and have started 8 hour intermittant fasting. I'm back on AMAT full strength as of today for a week. We'll see how it goes,but I'm hoping this could be a nice compromise to keep my dormant MAP in check while also minimizing AMAT side effects. Other than the joint pain now and the initial flu-like symptoms, I have had no other side effects on AMAT.

It's all about balance, and buying time for me. I think some cool therapies will be coming. RedHill is a great option, plus Qu with their SSI looks interesting. If we could get the Dietzia and EpiBro research going, they may pan out as well. Plus, there's a lot of dietary and natural options being looked into that could support immune health. I doubt I'd ever try MTX. It would feel like going backwards to me. I don't think the immunosuppressants are very effective, and am nervous about the side effects of that one in particular. A course of prednisone is what I may fall back to if needed.

Glad you like Human Para. I try. I just wnat to provide the resources for people that I had to hunt so hard for initially, and it's ballooned into a platform for all sorts of different research groups around the world. Many positive things coming out of that effort, and it's a great team. Hoping to start funding research VERY soon. Lots of legal junk to wade through in running a non-profit, but the MAP and other pathogenic research is the most promising stuff I see out there for CD, along with therapies that will rehab the broken immune system. We'll kick CD eventually! I'd rather it be sooner than later. 

Let me know how you do with your testing.


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## Crohn2357

OleJ, I am on 6mp. 

Keep in mind that I have no medical training; I am researching this stuff because I may use the anti-MAP antibiotics in the near future. I wouldn't mind the short term effects of the antibiotics because in that case the benefits generally outweigh the risks; but I am not sure how the antibiotics would affect me in the long term.

Different cytotoxic agents may exert cytotoxicity through different mechanisms.

The side effects depend on the dosage and the individual. They don't have to be acute reactions, just taking a drug that has cytotoxic effects is problematic on its own. Again, I wouldn't mind it on a short period of time, like we use them to treat common infections; but how these affect you in the long term is what I wonder. Because, AFAIK, there aren't a great knowledge on the long term effects of these.

Clarithromycin is a macrolide antibiotic. The other two are part of the drugs called antimycobacterials.

I haven't read the full text of the Selby study, so I do not know the details of it.


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## Deleted member 431298

Crohn2357: Thanks for clearing that up. I have no medical training either, and ultimately I would leave decisions such as therapeautic effects vs. side effects to the GI, should I go forward and try to get on AMAT. At least you tolerate 6MP, that's a good thing. (I didn't).

Irishgirl: Thanks for the honest update. I really hope the  weekly on/off cycle will give you both pain relief and remission. Let us know how you do. Yeah, it seems something in CD research is about to pay off. Now it's on to reading about the Dietzia and EpiBro research you mention, both are new words to me


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## Connor

Hi everyone, I'm new here, but not new to this subject. I was asked to join this forum so I could post my MAP story here.

I have ulcerative colitis, not crohn's, so my experience may or may not be relevant to others. My UC has been refractory to all modern drugs. The only other drug I am taking that has good result is Low Dose Naltrexone. My GI doctor has me on Entyvio and it only sort of works. If AMAT helps me more, I will stop Entyvio because its long-term side effects are gnarly. 

MAP was identified in my blood by blood culture in August 2017. I will be starting the AMAT protocol on November 1st 2017, consisting of: clarithromycin 250mg TID, rifampin 300mg BID, clofazimine 100mg QID

All of the scare research in this thread about the effects of the antibiotics are kind of inappropriate, in my opinion. If you look at the list of side effects of all the commonly accepted IBD drugs, the list is very large. Treating IBD in general carries some danger, but the disease is worse. I would rather risk side effects than have my bowel removed. 

Most of the macrolide side effects are dependent on your individual metabolism. If you tend to do poorly on modern drugs in general, then you are more likely going to experience intolerance symptoms. The other issue is the modern research does not adequately differentiate between true intolerance and die off symptoms. A lot of people really suffer in the first 3 days - 1 month of AMAT therapy and it's because their body's flora are going through massive shifts in the presence of these antibiotics, not to mention the primary pathogen itself dying off. If you have no other maintenance protocols in your life like diet, probiotics, herbal medicines, etc... then you will probably suffer more. I would not do AMAT on its own with no other support. 

You can titrate your dosages upwards, starting at a small dose, or you can start at full dose. The former is usually recommended. If titrating and giving it some time does not lead to improvement, then these medicines may not be for you.

The rare side effects stated in this thread almost never happen, and are usually accompanied by other effects first. If you have any body awareness whatsoever you're going to abandon ship before something crazy happens. You can do all the scary research you want and take it into account, but at some point you're going to have to accept the unknown and try the meds if you want to have a hope of getting better.

I refuse to let them to take my bowel just because they are too ignorant to really treat this disease. I won't do it. I respect other people's choices so don't take it personally. But I have witnessed so much terrible incompetence in the treatment of IBD that I can hardly endure another moment of it. Maybe I just live in a bad part of the world for treating IBD, but it is worth finding an alternative cure just to get away from these sociopaths.

My GI wants nothing to do with the AMAT protocol. Luckily I have an understanding GP who will do it for me. Even so, I am basically doing a self-directed treatment here because the medical system is totally oblivious to the work of Borody and Chamberlin. All my main supports come from the AMAT community online. There are a few doctors in the world who can give us some guiding advice, but we are really on our own. We don't need to see hundreds of scary research studies on macrolides, thank you. We are pioneers in IBD treatment -- we know that we're off the grid and that you don't support us. But nothing will stop me from trying this, nothing. I have a proven infectious disease in my body and the fact that modern doctors won't look at it is, to me, a cardinal sin. I want it out of me. 

The more people who try this and get better, the more we can finally start helping people. Colostomies and resections can be a thing of the past. It seems like every major breakthrough in the way we approach disease comes from outsiders who were shunned but took the risk anyway.


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## Deleted member 431298

Thank you for joining Conner, and for sharing your story, your thoughts, and your research. 
It's a good point that the list of side effect alone should not necessarily disqualify trying AMAT, but at least for my part being followed by someone who knows what he/she is doing would definately be reassuring if I am to start. As you write, it is a matter of personal preference. To be fair, I don't think it is Crohn2357's agenda to do scare us all, my guess is he just wants as much as possible on the table. 

I second your observation on GI's. For a year I have tried to get my GI to at least read the re-analysis of the Selby study, and see the informative lecture from Dr. Behr, but he never did it. He did agree to confer with GI colleagues at another hospital regarding my positive MAP test. Only I never heard from him, and when I went to the hospital to have blood drawn for another test, the GI nurse told me he has quit. So at the moment I am without a GI, with the prospect of getting a new one who most likely has not read any of the recent publications on the link between IBD and MAP.

For those of us who are seriously considering AMAT, updates on how you do going forward will be appriciated. Lastly, I could imagine there are UC patients out there who would also be interested to hear if this can have an effect given your diagnosis.


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## Connor

I was going to post a link to a study about MAP and UC but I can't post it until I've made 10 posts or more. Weird policy, but OK. 

I've heard from some AMAT doctors and Crohn's patients that UC is caused by something else and that MAP theory is not the focus. But then I have come across UC patients who have used AMAT to achieve remission, and I have read studies like the one I was about to post that link MAP to UC.

Bottom line... there is MAP in my system and my UC is not responding to treatment, so I might as well try this. It's suspected that UC patients were infected later in life or with a smaller concentration, whereas Crohn's patients had a higher loading dose of mycobacteria or they were infected as children.

My blood culture shows my MAP concentration is small compared to the Crohn's patients I've talked to. My body is very clean, I live a very organic lifestyle and I am sensitive to contamination across the board. It may be that even a small number of these organisms were enough to make my body flip out. I ate whatever I wanted and lead a normal life until I was 29 and then all hell broke loose. I spent 2 years living in Asia and got very sick many times there, so for me the infectious connection is obvious. 

In cattle, young calves are infected by their mother's milk, but they don't develop Johne's disease (the cow equivalent of Crohn's) until adulthood, so there is a delayed reaction. Same as in humans. The main distinguishing features between human and cattle versions is that in cattle, we can find MAP in bowel biopsies but in humans it's not observable in the bowel tissue itself. It may be in our lymph tissue and blood instead, things that the bowel is rich in. 

Either way, with a remission rate of higher than 50%, AMAT therapy is still proving to be better than all the crappy immunosupressive drugs they have us on. I guess AMAT therapy is not as profitable compared to the tens of thousands (sometimes hundreds of thousands) of dollars people spend on immune suppression for IBD every year.

The key factor is that MAP is everywhere. It's in water, soil and air. Everyone alive on planet earth comes into contact with it, but not usually in significant numbers, nor do they develop any kinds of symptoms. So there may be an immune deficiency component that allows us to get infected. I know for myself I was immune compromised the entire time I lived in Asia, with constant GI distress. It's possible that allowed MAP to take hold.


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## Connor

P.S. Sorry if I got a little short about the "danger" studies. I have been researching the ins and out of this topic for 6 months or so. I have a scientific background. Despite all this research, I still feel unprepared to start taking the medication. If more doctors were doing this, there would be more clinical experience to rely upon. Instead all I have to go on is research and the stories of other patients who have done AMAT.

At some point you have to take that leap of faith and dive into the unknown. All the research in the world can't tell you what your body is going to do, nor can it predict biological systems perfectly. Our knowledge of the body and disease is still very imperfect. 

I take the plunge in just a few days. I will post my progress, though maybe not at first. The blow by blow might scare people. I expect at least the first week to not be very fun.


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## irishgal

I agree Connor - it especially irks me when mpthe mainstream GI community dismisses the risks of biologics (like untreatable Tcell cancer!) but freaks out when I'm going to take antibiotics that have been used for decades in millions of patients. I think for normal people, with healthy gut flora, antibiotics can be VERY bad. I think we're only figuring out how bad thta is now, and even at low levels in food they are bad. But for CD (and maybe UC patients) our flora is junk. It's hurting us. So antibiotics give us relief and stop whatever is destroying us. It's hard to know exactly what role the microbiome plays alongside MAP. We just need more research to answer some of the critical questions, but as you mention, treating IBD is a risk analysis. Uncontrolled disease and inflammation is probably worse than the side effects of any treatment, and I wish the docs wouldn't get so comfortable with the biologics. It's like they've been brainwashed by BigPharma and it's been beaten into normalcy due to the pervasiveness of these treatments at seminars. Side effects have been minimized.

For me, I was sick with colds and viruses constantly while on biologics. The printed material on both Remi and Humira clearly state that's a big deal, and to tell your doc. I'd do that, and they'd just tell me I have a cold. It was no big deal. But I got multiple rounds of sinus infections and bronchitis. It didn't even phase them. I quit telling them. Plus, it did nothing for my CD. AMAT is absolutely a viable treatment, and I'm hoping RedHill will prove that once and for all. Good luck with your journey! I don't envy you those first few weeks.


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## Crohn2357

If you think the only negative effect of antibiotics worth considering is their ability to manipulate your microbiome, then you need to read and think a lot. 

“People almost invariably arrive at their beliefs not on the basis of proof but on the basis of what they find attractive.” 
― Blaise Pascal

If you want to make a proper risk analysis, you need to study the risks.

Being reactive to questioning has always been a sign of stupidity. I have no motives to change yours, so I will not give any further replies to your comments.


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## Deleted member 431298

Six years ago, while on Humira, my creatinine levels suddently started to rise. A biopsy revealed chronic changes to both kidneys (interstitial nephritis). Could be an extraintestinal manifestation of CD, but most likely a side effect of the biologic, according to my specialist.
Better get off it, the GI said. So I did and got quite sick very quickly. OK, the GI said. Lets try Remicade. OK I said.
A year later, I was sitting the chair reading while the Remi was dripping through the IV i heard a "Thump" and the person next to me fell over in spasms. The nurses picked her up, tilted the chair backwards, stopped the IV and gave her an injection. Slowly she came to. She was taken to another room, the rest of us continued.
One year after that, creatinine started to rise again. Estimated kidney function now 40%. Then I stopped biologics for good. I have managed to do without, but that's another story.

My point is this: Bring ignorant about side effects is one thing, making a judgement call between risk of side effects and therapeutic benefit is another. I believe Conner is doing the latter. 

Sure, the antibiotics could result in some unwanted cytotoxic reaction, but hey, we are already in a place where there are certain risks no matter what route we go, whether it be biologics, sterorids, AMAT, cancer drugs or nothing at all.


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## irishgal

Crohn2357 - I assume your vitriol is directed at me? And now that I'm reacting (for the benefit of all on this thread) I guess I'm "stupid?" 

I never mentioned that I believed microbiome shifts were the only negative effect of long term antibiotics. I don't know where you got that. My above comment was specifically questioning the effect of antibiotics on gut bacteria as related to the interplay of MAP. I know long term antibiotics can have significant side effects as you mentioned. But so can all other CD treatments, and when the patient is out of traditional options, most are willing to assume more risk since untreated CD presents a serious risk as well. 

Not really sure why you started this thread if you are stressing the risks of antibiotics and not looking at the benefits as well. And no need to get nasty. This is an open dialogue between patients who are suffering and want to learn. I've been lucky that AMAT has healed me and I haven't had serious permanent side effects. To get a prescription, presumably every patient would have to discuss the risks and benefits of AMAT with their doc, and also be continuously monitored for side effects. Don't really see what your problem is, but seems as if you have an ax to grind against AMAT.


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## Deleted member 431298

May I suggest that we have a look at the topic at hand from a slightly different approach: What do the experts say about the side effect profile of AMAT, and what are the popular descriptions of the side effects profile of the AMAT drugs? 
One statement from William Chamberlain, commenting the Selby et. al. study:

_[...] The data support another interpretation: AMAT provides a more effective treatment regimen with a more favorable side effect profile than current conventional therapy. [...] _

Granted, Chamberlain treats patients with AMAT himself, so he may be biased, but it does seem like the Selby study at least did not report any severe side effects.

AMAT drug side effects, as written on www.medicinenet.com:
(Note: any cocktail effect is not taken into consideration)

*Side effects for clofazimine*
_More common side effects include: loss of appetite, diarrhea, nausea, vomiting, dry skin and discoloration (from pink to brownish-black) of the skin, stools, urine, saliva, sweat, tears or lining of the eyelids. Other side effects reported are changes in taste, dry or irritated eyes, headache, fever, increased blood sugar and an increased sensitivity to sunlight.

*Clarithromycin* is generally is well tolerated, and side effects usually are mild and transient. Common side effects of clarithromycin are: nausea, diarrhea, abnormal taste, dyspepsia, abdominal pain and headache.
Other important side effects which are rare, but serious include:
liver failure, hearing loss, and seizures.
Clarithromycin should be avoided by patients known to be allergic to clarithromycin or other chemically-related macrolide antibiotics, such as erythromycin. Treatment with clarithromycin and other antibiotics can alter the normal bacteria flora of the colon and permit overgrowth of C. difficile, a bacterium responsible for pseudomembranous colitis. Patients who develop pseudomembranous colitis as a result of antibiotics treatment may experience diarrhea, abdominal pain, fever, and sometimes even shock.

*Rifabutin*:
side effects: Diarrhea, stomach upset, changes in taste, or nausea/vomiting may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.This medication may cause urine, sweat, saliva, or tears to turn brown-orange. This effect is harmless and will disappear when the medication is stopped. However, dentures and contact lenses may be permanently stained. Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects. Tell your doctor immediately if any of these rare but serious side effects occur: easy bleeding/bruising, signs of a new infection (such as fever, persistent sore throat/cough), muscle weakness/pain, joint pain/swelling, eye pain/redness, vision problems, chest pain/pressure, persistent nausea/vomiting, unusual weakness/tiredness, dark urine, yellowing eyes/skin.This medication may rarely cause a severe intestinal condition (Clostridium difficile-associated diarrhea) due to a type of resistant bacteria. This condition may occur during treatment or weeks to months after treatment has stopped. Do not use anti-diarrhea products or narcotic pain medications if you have any of the following symptoms because these products may make them worse. Tell your doctor immediately if you develop: persistent diarrhea, abdominal or stomach pain/cramping, blood/mucus in your stool.A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects._


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## irishgal

Love it Ole. Very informative. Knowing how they react together though is important. I know from the research done by Naser and crew in vitro that the triple combo in RHB104 has some synergistic type effect. Studies posted below. I've also been told to space the rifampin as far from the clarithromycin as possible since it can speed up the clarithro metabolism and lower the clinical level in the bloodstream. I believe the RedHill pill uses a buffering system with PEG or possibly a capsule inside a capsule (the patent was very hard to understand!) to combat this effect.

The AMAT docs have told me that the side effects of AMAT, while possible, are not as serious or common as those of biologics. I know they're probably biased, but they've also treated a lot of patients. Long term is an issue that concerns me, but I know some TB patients take them for years, so at least there is that data available, as well as the few reported of CD patients. As has been mentioned, it's a risk/benefit analysis to discuss with your docs.


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## Crohn2357

http://www.medicaldaily.com/antibio...ody-are-medicines-helping-patients-all-247367
https://www.ncbi.nlm.nih.gov/pubmed...ion+and+oxidative+damage+in+Mammalian+cells,”
http://stm.sciencemag.org/content/6/238/238ec92
https://www.nature.com/nbt/journal/v31/n5/full/nbt.2574.html

These articles suggest that bactericidal antibiotics[1] may increase oxidative stress. In addition to supplementing with probiotics, it might be a good idea to take antioxidants and eat an especially anti-oxidant rich diet if you are using the long term antibiotic therapy. This might help fighting with the ROS build up.


[1]: General info on this: https://courses.lumenlearning.com/boundless-microbiology/chapter/overview-of-antimicrobial-therapy/

Antimycobacterial agents were evaluated with respect to their bacteriostatic activity (growth inhibition) versus the bactericidal activity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140486/


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## Connor

....


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## Deleted member 431298

Short update to my MAP-levels-trend-experiment:
The MAP culturing process has now started. At the same time the blood was drawn, a week ago, I had a Calprotectin test done. Results just came back elevated: 285 ug/g. That is consistent with my symptoms. Tests earlier this year while on Methotrexate have been <100 ug/g, indicating remission. 
After the tests I started Methotrexate 12.5mg/week orally. Diarrhea has already gone, and I feel better. 
It will be very interesting for me to learn if the flare has led to an increased number of M. Paratuberculosis bacteria in my blood. I will post the results when they arrive.

In the meantime I found a very interesting study testing the action of Methotrexate and 6-MP on MAP in vitro (in the lab). The study found Methotrexate to inhibit MAP growth almost as effectively as Clarithomycin, 6-MP somewhat less.  
Maybe Methotrexate should also be called Anti-MAP therapy? 

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1779805/#!po=46.8750

The study propose that the primary action of Methotrexate and 6-MP in IBD to kill MAP bacteria:
_
Both methotrexate and 6-MP interfere with DNA replication. Methotrexate acts by inhibiting dihydrofolate reductase, folate generation and the consequent production of adenine.[12] The mechanism of action of 6-MP is to substitute for guanine in DNA replication.[12] Because prokaryotes (simple cells, such as bacteria, OleJ's comment) must synthesize their own folic acid, they should be more susceptible to folate inhibition than eukaryotes. (More complex cells, such as human cells, OleJ's comment)
_


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## Deleted member 431298

Adverse events during two years of AMAT treatment of around 100 patients in the 2007 Selby study

_Adverse Events
Overall, the treatment was well tolerated; only 16
subjects were withdrawn because of an adverse event: 8 in
each group, including 5 each in the induction phase.
Several adverse events were significantly more common
in the antibiotic group than the placebo group during
the induction phase: abnormal liver function (2.3% vs
0.3%, respectively), vaginal candidiasis (4.0% vs 0.8%, respectively),
abdominal distention (3.4% vs 0.8%, respectively),
myalgia (2.3% vs 0.3%, respectively), and urine
discoloration (2.8% vs 0.3%, respectively). Between weeks
17 and 52, arthralgia (3.5% vs 1.2%, respectively) and
tooth discolouration (2.3% vs 0.2%, respectively) were the
only adverse events significantly more common in those
on antibiotics than on placebo. The number needed to
harm during the induction phase was 77 and, for the
whole study, 40._


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## Guerrero

Toot discolouration, outch not nice :S

Do you have an idea of the adverse events level with biologics?


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## Deleted member 431298

Guerrero, I know there are reports of allergic reactions and serious infections but don't have the statistics. Also, I suspect not all adverse effects are registered, because there is no way of proving that Remicade caused them. I got a very serious infection in my kidneys, and it is unclear if that came from Anti-TNFa or Crohns. It has to be said I had been on Remicade and later Humira constantly since year 2000.


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## Deleted member 431298

Another note: Could the Redhill Anti-MAP therapy study be flawed??
Learning that Methotrexate (MTX) and 6-MP have Anti-Map effects in vitro made me think if they are allowed as a supplemental treatment in the Redhill Study. And--- YES THEY ARE!

The same researcher (Greenstein) who reported the Anti-MAP effect of MTX and 6-MP(I linked to the study above) has actually warned about this in this commentary. 
This is bad news. It could mean the therapeutic effect of the Anti-MAP antibiotics do not stand out over the other drugs given to both arms in the study.


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## irishgal

Ole - that has been a common issue and came up at the Philly conference. There was some debate on Dr. Greenstein's methods as well, which hasn't been reproduced. Ultimately, I don't think you see a lot of patients jumping up and down saying their CD was healed by 6MP or MTX, though they both do seem to help some. If you add on Rhb-104 to those, and people do incredibly well, then you'd have to conclude it was the RHB that was doing the bulk of the healing. Keep in mind, a lot of the patients in the RedHill trial had already been on a therapy for a while and still had moderate to severe CD to qualify for the study. So it's not like their current therapy is doing all that much.


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## crohnsufferer

Hello

I am a long term Crohn’s sufferer and I am looking for information about Dr Jeremy Sanderson ant the anti-MAP therapy. After trying and failing immunosuppression I read about this new therapy in the Human Para Foundation website where Dr Sanderson’s was mentioned. I understand he is one of the few doctors in the world who provide anti-MAP therapy. I would be grateful if anybody who is being treated or has been treated by him could share their experience so I can get some feedback before I decide whether to make an appointment. I am especially interested in hearing from people who see him in private and/or from outside the UK. I am not a UK resident so things would be more complicated for me.

Thank you

(I hope I posted in the right thread)


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## irishgal

Are you in Europe Crohnsufferer? Have you looked for docs in your local area? I know Dr. Sanderson sees private patients at the Shard building location and I've heard good things.


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## Crohn2357

Crohn2357 said:


> http://www.medicaldaily.com/antibio...ody-are-medicines-helping-patients-all-247367
> https://www.ncbi.nlm.nih.gov/pubmed...ion+and+oxidative+damage+in+Mammalian+cells,”
> http://stm.sciencemag.org/content/6/238/238ec92
> https://www.nature.com/nbt/journal/v31/n5/full/nbt.2574.html
> 
> These articles suggest that bactericidal antibiotics[1] may increase oxidative stress. In addition to supplementing with probiotics, it might be a good idea to take antioxidants and eat an especially anti-oxidant rich diet if you are using the long term antibiotic therapy. This might help fighting with the ROS build up.
> 
> 
> [1]: General info on this: https://courses.lumenlearning.com/boundless-microbiology/chapter/overview-of-antimicrobial-therapy/
> 
> Antimycobacterial agents were evaluated with respect to their bacteriostatic activity (growth inhibition) versus the bactericidal activity: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1140486/


"How do antibiotics affect human mitochondrial function, especially on the long term?" I've been wondering about this for some time.

First, read this: Cooper GM. The Cell: A Molecular Approach. 2nd edition. Sunderland (MA): Sinauer Associates; 2000. The Origin and Evolution of Cells.

Endosymbiosis: https://en.wikipedia.org/wiki/Symbiogenesis
http://biology-pages.info/E/Endosymbiosis.html
https://evolution.berkeley.edu/evolibrary/article/_0_0/endosymbiosis_04




> Indeed, mitochondria, the organelles responsible for energy production in the cell, have bacteria-like DNA and other molecules, suggesting that mitochondria are the product of an ancient endosymbiotic event, in which a bacterium was engulfed by another cell. The important implication of this, said Ronald DePinho, president of the MD Anderson Cancer Centre in Houston, Texas, who also did not participate in the research, is that “drugs targeted to [bacterial] physiology might also impinge on mitochondrial biology.”


and a comment on this report: 





> In additon to the disruption of normal ROS signalling pathways mentioned in this paper many antibiotics have two other deleterious effects in human cells. They decrease respiratory competence and shift cell populations to aerobic glycolysis (the Warburg effect) resulting in localized lactic acidosis and a microenviroment favorable to tumor formation, tissue invasion and metastasis. In addition increased poduction of ROS is mutagenic to both nDNA and mtDNA destabilizing both genomes, decreasing mitochondrial survellance and clearing of tumorigenic karyotypes in the nucleus  by the intrinsic apoptotic pathway, both hallmark features of cancer. I suggest (in agreement with many other investigators) that such antibiotics are carcinogenic and thus the findings reported here are very clinically relevant especially when administered for chronic infection. We need to find alternative antimicrobial therapies for non life threatening infections that do not harm these patients.


http://www.the-scientist.com/?articles.view/articleNo/36329/title/The-Downside-of-Antibiotics-/

From:http://www.the-scientist.com/?artic.../Widely-Used-Antibiotics-Affect-Mitochondria/
https://medicalxpress.com/news/2015-03-antibiotics-unexpected-effects-mitochondria.html   (the same story)

https://biology.stackexchange.com/questions/9570/why-dont-antibiotics-affect-mitochondria
https://biology.stackexchange.com/q...cin-not-affect-human-mitochondria/48004#48004

These are discussed in the context of healthy populations; but when you think about the findings on Crohn's and mitochondrial dysfunction, this becomes even more important.

Mitochondrial dysfunction in inflammatory bowel disease 
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4589667/

Mitochondrial dysfunction, persistent oxidative damage, and catalase inhibition in immune cells of naïve and treated Crohn's disease.
https://www.ncbi.nlm.nih.gov/pubmed/19637347

Next two articles (below) sort of explain why anti-tnf's work in Crohn's, and why they do better than the traditional immunosuppressants on tissue healing:

Role of oxidative stress and antioxidant enzymes in Crohn’s disease
http://www.biochemsoctrans.org/content/ppbiost/39/4/1102.full.pdf

Mitochondrial Dysfunction in a Patient with Crohn Disease: Possible Role in Pathogenesis
http://journals.lww.com/jpgn/Fullte...l_Dysfunction_in_a_Patient_with_Crohn.14.aspx

"Gene that affects cell power supply may hold key to bowel disease"
https://www.sciencedaily.com/releases/2017/05/170517101159.htm

"Studying the role of damaged mitochondria in causing Inflammatory Bowel Disease."
https://www.crohnsandcolitis.org.uk...vestigating-the-faulty-batteries-inside-cells


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## crohnsufferer

Hi irishgal,
yes I am in Europe and unfortunately there are no doctors in my area who prescribe anti-MAP therapy. It won't be too difficult for me to go to London but it is expensive so I wanted to make sure I found the right doctor and that he is good at what he does.


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## Connor

I suggest everyone ignore Crohn2357. He's just here to troll with scary research and not really have a genuine discussion about the clinical experiences with AMAT. I wish the mods would do something about it. What matters more is what IBD patients on AMAT are saying. Random research about the dangers of antibiotics is not very helpful. We need to look at the clinical data. 

As for me, an update... I started AMAT 4 days ago. The herx reaction is very intense. Mind you, I have ulcerative colitis and not CD so my experience may be different. I started at full dose - 500mg clarithromycin 2x daily, clofazimine 100mg 1x daily, rifampin 300mg 2x daily. 

The reason why I chose to start at full dose is because the most experienced doctors with AMAT recommend it in order to avoid bacterial resistance. 

I'm also taking LDN 3mg. 

So far the harshest effects are on my bowels. I was already at the tail end of a flare but now my bleeding and pain have increased. However, I'm not flaring. I think the drugs are just really irritating to the GI. The other effect I'm noticing is that my face is extremely dry and inflamed, which I have heard is a side effect of clofaz, but it may also be a herx reaction. Either way it's too soon to tell. I've been moisturizing 3-4 times a day and it doesn't seem to be helping. I am also a lot more dry in general.

I am getting blood work done this afternoon to see where my body is at. My biggest concern right now is that my hemoglobin was already on the lower side before this, and if it's getting too low from the increased bleeding I may have to consider stopping. However, if the bleeding is a result of a herx, it should get better after these first two weeks. The general suggestion I've been given is that if I can tolerate the meds for 1 month, but if after that 1 month I'm not improving, then I should probably stop. 

I've upped my probiotics a lot. There are mixed opinions on this. Some say to wait for the initial die off to stop before adding pros, others say you need to be doing pros between antibiotic doses to avoid c. diff. The clinical literature on AMAT and c. diff seems to indicate that it's actually rather rare, unless you were already prone to it.

Two days ago I received a glutathione IV from a naturopath, and I have started taking milk thistle twice daily. I'm trying to give my body as much liver protection and detoxing capacity as I can.

I considered starting with levofloxacin instead of clofazimine but the black box warning about tendon ruptures from the fluoroquinolone family of drugs made me opt against it. It does tendon damage to 100% of people who take it, it's just that in some the damage manifests as actual symptoms. I've read many horror stories. I would not take a fluoroquinolone unless it's literally a life and death situation. Clofazimine on the other hand is also a very harsh drug. The clinical data shows 50% of people who take it end up stopping it. My intuitive sense is that, of the three I'm taking, clofaz is causing the most problems. 

On the whole though, my symptoms are not as bad as they could be. No nausea, thank god. For me nausea is a deal breaker. So far it's lower GI symptoms + face dryness, and if these get better as time goes on then I think I can live with this protocol.

Down the road I'm also looking into fecal transplant. UC'ers tend to do well with those, and I'll need to replenish my bowel flora after all these antibiotics.


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## Connor

My mycobacterial infection was diagnosed by Otakaro Lab in New Zealand. Right now it's the most accurate method available. The Crohn's Vaccine development program is also creating an accompanying rapid MAP test that will be available in the future, but for now Otakaro is the best we've got. There are other labs in the world that test for MAP using blood PCR assays, but they aren't as accurate. You really need to culture blood to find the MAP, and MAP has very specific requirements to be seen in a culture. 

It's difficult in general to run a PCR assay on MAP because researchers are still figuring out the best RNA sequences for identifying it. Otarko has identified active mycobacteria in my blood, but whether or not they are MAP is not certain. However, because the infection is active and my IBD is refractory, I decided to give AMAT a try anyway. The difficulty with UC and MAP is that UC patients tend to have the same numbers of mycobacteria as the healthy control group, so MAP may not be the causative factor of UC, but rather a complicating factor. Most healthy people have some mycobacteria in their bodies. They are ubiquitous in the environment. However, people with IBD have some kind of immune deficiency which can't prevent the mycos from causing harm, especially in CD patients. However, some UC patients go into remission with AMAT. I think if you're a CD patient you have a much higher chance of this successfully working.

I'll post more updates later in my treatment.


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## irishgal

Good luck with your treatment Connor. Let us now how you do. I know the beginning is pretty rough, especially if you start full strength. I did as well, mostly because that's what my doc told me, and I didn't know any better. But with my case, it got all of the horrible effects out of the way in the beginning during the die off and I think it killed any MAP that was active at the time, which I think was a bunch per my culture (also from Otakaro.) Crossing my fingers it works spectacularly for you!


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## Deleted member 431298

Good luck Conner, and thank you for updating us here. 
Crohnssufferer: I also considered contacting Dr. Jeremy Sanderson, I even got my GI to write up a referral document (which is required to get an appointment) but I am also afraid of the cost, and I want to get the results of a blood culture test first. I will update you if I go ahead.
Irishgal - Good to hear is topic was covered in Philly. In an optimal study design though it seems a solid MAP culture test of subjects prior to AMAT, and more research on the effect of MTX and 6MP would have been nice gauges for the efficacy.


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## Connor

Just a little update. I'm one week in and having a hard time. My bowels are extremely irritated by the antibiotics. I had to cut out clofazimine for a little while and just stick to clarithro and rifa. Even so, I am bleeding a lot and my CRP went from less than 1 to 35. I'm getting an iron IV today. 

As a result I've had to start prednisone again. I'm doing a low dose of 10mg, and I'm taking DHEA with it. Last year I had to do a different triple therapy to get rid of b. hominis and aeromonas, and within two days of taking abx for it my bowels became so healthy. But this time... I'm not so sure.

I'm giving it the standard 2 weeks to see if it's just die off or I really can't tolerate this therapy. So far I am leaning to the latter. My symptoms are a throw-back to 2 months ago, although I don't seem to be flaring for real. It just seems like major irritation of the mucosa that has barely had a chance to heal.

I'd recommend that anyone starting this therapy who knows they are sensitive to abx should do the ramping up method rather than starting at full dose. Other than my bowels, I have no other intolerance symptoms. No nausea, nothing.


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## Deleted member 431298

Conner, thank you so much for your honest update. Information like this is really valuable to me, and I presume, to others following this thread. I am sorry to hear you are having such a hard time. I cross my fingers it is the herx reaction and/or your system adjusting to the antibiotics, and the symptoms will fade. Keep us posted if able, and good luck.


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## Deleted member 431298

Irishgal, I wonder if you know why the Greenstein study on 6MP/MTX as MAP inhibitors was not reproduced?
Was it because no one ever tried?
Or was it that others tried but were unable to get the same results?

EDITED/ADDED:
I came across this intersting study about anaerobic adaptation of MAP  (from 2017)

The conclusion says:

_[...] a number of investigators have demonstrated dose-dependent inhibition of MAP in culture by a number of anti-inflammatory drugs including methotrexate and 6-mercaptopurine [37, 38, 39, 40, 41, 42, 43, 44]. As a result, Greenstein et al. postulated that treatment of patients with inflammatory bowel disease with methotrexate and 6-mercaptopurine may result in inhibition of MAP and secondarily a decrease in pro-inflammatory cytokines [42]. In the current study, testing of anti-inflammatory drugs was beyond the scope of this project. However, future studies are planned which will determine the activity of anti-inflammatory drugs against MAP under both aerobic and anaerobic conditions_

I will read up on the refs. 37-44 to see what they say about this matter.

Apart from this observation re. MAP and 6MP/MTS, the article is a very interesting read. The researchers suggest the reason AMAT is unable to clear the MAP infection completely may be that the MAP bacteria can take on an anaerobic state, where the drugs cannot reach the bacteria.


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## irishgal

Ole - this is a bit of heresay, but I believe it was tried and was not able to be reproduced. Something about the lab equipment used??


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## irishgal

And if you want to watch Dr. Parrish's presentation on her work you mentioned above, about anaerobic adaptation of MAP, it's on the site. She was supposed to present in Philly, but had to cancel at the last minute. However, she kindly recorded her talk with a colleague and provided it to us to post! And they are out of Johns Hopkins.
https://humanpara.org/2017-parrish-video/

MAP is a pretty great mutator. Very hard to kill. This is the type of stuff you see with TB.


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## Deleted member 431298

I watched to video with Dr. Perrish, thank you for pointing to that. Very exiting stuff, and I am encouraged to learn experienced microbiologists and TB specialists like her (and Marcel Behr) are doing research on the MAP-CD connection.

Irishgal: Out of curiosity - did your doctor (or yourself) ever consider adding an anaerobically effective antibiotics (metronidazole) to the regimen? I am in no way competent to suggest whether it would be a good idea...

*A few thoughts on Methotrexate and the Jarisch-Herxheimer reaction*
Then on to an anecdote about myself, which leads me to speculate whether MTX can result in a (small) Jerisch-Herxheimer reaction. So I took a break from MTX monotherapy over the last two month, to see if if my MAP levels would increase. I got CD symptoms, elevated calprotectin, shipped of blood for MAP culturing, and two weeks ago I started MTX again. 

Yesterday morning I took my second dose of 12,5mg once a week. I felt weak towards evening time, went to bed early, and woke up at 2:30AM feeling like crap. Low grade fever, nausea, and stomach discomfort. Between 2:30 and 4:30AM I went  to the toilet like six times and almost vomited. 
That is so strange, I thought. Usually that dose would result in a lack of appetite for half a day or so, maybe some nausea, but definitely nothing like this, and never a sudden onset of diarrhea and urgency.
Interestingly I had a similar reaction, and an really awful night a week ago- the night following the first dose of MTX after restarting. 
Last week I did not think much of it, and apart from a truly shitty appx. 24 hours, the following days I felt fine with normal BM's. 

But last night, when the symptoms reoccurred, I started speculating about why I got so fierce symptoms from MTX, and I thought of Conner's description of what is possibly a Jerisch- Herxheimer reaction in this thread.

So last night I looked into the Herx reaction, and found the article: Jarisch–Herxheimer reaction: paradoxical worsening of tuberculosis chorioretinitis following initiation of antituberculous therapy

In the article they describe that Prednisolone dampens the symptoms, so at around 4:30 I took 12,5 mg prednisolone.
About an hour later I felt the stomach settle down, and I was able to go to sleep. This morning I feel fine, hungry, and my stomach is calm. It seems I have had quicker resolution of symptoms than last week, where I felt bad the following day too.

Although this is just an anecdote, I can't help but wonder if I am experiencing the Herx reaction because MTX is targeting more live MAP bacteria now that I have been off it for two month.


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## irishgal

Ole - I have actually had great success with flagyl over my 25 years of dealing with CD. It was the only thing that worked really well and I was on and off of it many times. I'd get much better, but then would have to come off and the CD would return. When I started AMAT, I figured it was better than flagyl since none of this research was available at the time. Now, Dr. Borody uses flagyl as a 4th sometime, or it's cousin tinidazole which I think is a safer alternative. Since flagyl causes nerve damage and other side effects, it's not safe for long term use, so if I relapse, a course of that will certainly be in the cards - maybe with clofaz. But I was doing so well at the time, I never thought about adding another antibiotic since I didn't want to mess with success. Still doing well, so no need to add more meds if the current ones are keeping the MAP under control.


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## BasedJawline

If rifaximin worked for me does that mean the anti map antis will also work?


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## irishgal

BasedJawline said:


> If rifaximin worked for me does that mean the anti map antis will also work?


Not necessarily. Rifaximin I think is for people with SIBO and IBS. It's in the same family as rifabutin and rifampin, so it could be a clue that you may have a MAP infection, but the best way to know for sure is to send a sample to Otakaro Pathways and get tested. If you come up with MAP, maybe your doc would consider AMAT on the premise that rifaximin worked well. If you've run out of all other therapies, it's an easier sell too.


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## Crohn2357

How do people who are using (or considering to use) the anti-map therapy find clofazimine?

This is an important issue.


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## irishgal

Crohn2357 said:


> How do people who are using (or considering to use) the anti-map therapy find clofazimine?
> 
> This is an important issue.


If you are in the US, you can get a script from your doctor and fill it at an online pharmacy in Canada using Pharmacy Checker. That's the easiest way, though I know a couple of people who get it from India and Switzerland. Not sure about other countries. I know it's very difficult to get if you live in Canada.


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## Deleted member 431298

To Conner:
How are you doing? Good I hope!. If you would consider giving us a heads up I'd be greatful. Cheers


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## Crohn2357

Do some patients use flagyl as part of the anti-map drug protocol?


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## Crohn2357

I am adding two links to this support group:

Anti-MAP treatment for Crohn's Disease

An Interview with Dr. T.J. Borody

Note that these are undated articles, and are most probably not new.


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## Crohn2357

irishgal said:


> If you are in the US, you can get a script from your doctor and fill it at an online pharmacy in Canada using Pharmacy Checker. That's the easiest way, though I know a couple of people who get it from India and *Switzerland*. Not sure about other countries. I know it's very difficult to get if you live in Canada.


This video shows the adress of a pharmacy in Switzerland which is said to have clofazimine. It can be seen at 14.25.


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## Crohn2357

Crohn’s Disease & MAP Frequently Asked Questions

Mycobacterium Avium subspecies Paratuberculosis (MAP)


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## Connor

OleJ said:


> To Conner:
> How are you doing? Good I hope!. If you would consider giving us a heads up I'd be greatful. Cheers


I'm 1 month in and all bleeding has stopped. Stools became formed so quickly that they are actually causing bleeding, but the bleeding is not related to UC. CRP is in normal range now. I can finally start to get off prednisone.

Because I stopped taking clofazimine, I am looking into a 3rd drug to replace it. I may use tinidazole, but I'm not sure yet. Even at low doses, I don't see how I could tolerate an azole drug for months. They're really hard on the body. 

There was a time a couple weeks back when I felt like my body was on toxic overload and I didn't know how to deal with it. My liver and kidneys felt sluggish. Then one day I was at the grocery store and I saw beet sauerkraut, unpasteurized, and I found myself craving it. I went home and literally ate half the jar, which is insanely fibrous for someone with UC.

Within a couple days my body aches and pains, skin issues, sluggishness and fatigue all died down. So now I have a bit every day. I think it's the glutathione in beets that must be helping. Glutathione scavenges the body for reactive oxygen species, which is what AMAT releases to kill organisms. 

Over all I am happy that I started AMAT and I seem to be tolerating it much better now. But man, the first couple of weeks were hell!


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## Deleted member 431298

Conner, I'm so glad to hear you are past the first rough week. Wish you smooth sailin' from now on 

To recap my story: was in remission this spring, on medication (calprotectin <100, no symptoms). Got a MAP culture test done that came back positive, but with very low numbers of live bacteria. Got off dairy and cow's meat and tried to taper and stop medication. Got sick in september (calprotectin close to 300, diarrhea). 

Latest news:
Sent of another blood sample for culturing a month ago while I was sick, before restarting medication - and it just came back positive, with significantly higher numbers of live bacterias present than the first test.
Food for thought...


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## Connor

The numbers are always higher during a flare because that's when they're active and reproducing. They create biofilms and peptidoglycans which induce inflammatory responses in the body.

During periods when you're healthy and strong they will be dormant and in smaller numbers.


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## Deleted member 431298

here's the results of the two tests compared. It would be very interesting to hear what other's results are / was (staining bacteria, pct. at 7 and 30 days).

[EDIT: WOW this was my post number 100  ]


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## Connor

That's a handy bar graph. I don't have something so visually laid out, though I guess when I get my second round of blood work cultured I will be able to draw comparisons. 

You have way more large forms than I did in my test, but I have UC and you have CD. The highest I had was 6%. If MAP is the reason for my UC, then it's crazy that my body is reacting to such small numbers. However, it would, given how sensitive my immune system has always been.

Can I ask where you got your culture done, Ole J?


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## Deleted member 431298

The test was done by Otakato Pathways in New Zealand. Where did you get yours done? If you do a second test I'd be really interested in knowing your MAP levels trend. Maybe initial value can be different based on your UC diagnosis and immune system, but I am guessing there should be a decline in numbers if MAP is a causative agent. 

In the conclusion of the test from may, they wrote:
_The overall appearance is similar to that seen in Crohn's disease, where the patient is in remission or on prolonged therapy._

In the conclusion of the test from october, they wrote:
_The overall appearance is similar to that seen in Crohn's disease where the patient may be on a sub-optimal therapy. There is some indication of growth suppression and no appreciable increase in ruptured forms._

The graphs are easy do draw in Excel if you know that program. I did it manually, filling cells with color to represent the bars.


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## Crohn2357

For patients who want to try (or learn more about) Anti-MAP therapy, Dr. Chamberlin says they "are building a private database of practitioners and will assist if possible". 

Full quote: 





> *Help! My doctor won't prescribe AMAT. What do I do?*
> This is currently one of the most common practical questions I get. First try providing your GI or general practice doctor with the Core Research Pack on this site, and then requesting that they consider prescribing AMAT once they are fully informed. Better still, have them view the videos on the website. Of course, I would be happy to evaluate you in my office in New Mexico if you are able to travel to see me. If that is impossible, check the RedHill trial sites for a location near you. There are supervising doctors at each site, many of whom have their own GI practices. They would be familiar with AMAT and would be able to discuss it with you. Alternatively, integrative or functional health doctors are generally open minded practitioners and many patients have had success once they are provided the research. If you have exhausted all of these options, please contact TheCrohnsInfection.org as we are building a private database of practitioners and will assist if possible.


Taken from: https://humanpara.org/anti-map-qa/

The link he gave has changed. To contact them, you should go to this link: http://humanpara.org/contact/


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## irishgal

Crohn2357- In regard to the above info about finding an AMAT doc, that is one of the biggest challenges people who want AMAT face now. Understandably, since it's not fully approved and considered off label, and we live in a fairly litigious society. Hopefully this is just a stop gap measure until RedHill is approved. 

And just as a little background, the website changed from The Crohns Infection to Human Para when it became an IRS nonprofit. Prior to that it was just some of us trying to put out good info to people who needed it, but we couldn't do much since we didn't have funding. Now, as a nonprofit we can do things like sponsor conferences and research, and give people tax credit for donations. We have the ability to actually move this forward as a legitimate organization. Also, we decided we wanted to focus more on MAP diseases and not just Crohn's, so that was another reason for the naming switch. 

We do in fact keep a private list of doctors around the world that patients contribute to since we get a LOT of inquiries from patients asking for a doctor in their area. The privacy is required because we certainly don't want anyone to get in trouble for prescribing off label. Also, prescribing AMAT is very situational, so a doc may not want to be known for prescribing AMAT and have patients demand that if it's not right for their case. The best we can offer is that these docs may have some familiarity with MAP science and may be open to reading the research. Integrative health docs also seem to be more open minded as well.


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## Crohn2357

irishgal -  I agree with the necessity of the precautions you have taken.

For patients (or loved ones) who are reading this support group: If you have tried all the conventional medications without achieving remission, you have a greater chance of using off label treatments. At that point, I think it would be wise to send your blood samples to Otakaro Pathways and get tested for MAP. If the test result comes back positive, at least you and your doctor will have another justification (the other being having a treatment-reftactory disease) for using an off-label treatment (like anti-MAP therapy).  

According to Dr. Chamberlin, "there is a 20 year body of peer reviewed research which indicates that AMAT is as effective as other Crohn’s therapies in inducing remission"[1]. In addition to your blood culture report, show your doctor the compiled literature and resources on the MAP hypothesis[2] .

That's my two cents.

[1]: Source: https://humanpara.org/anti-map-qa/

[2]: You can find these on the first post of this support group.


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## Deleted member 431298

Connor said:


> You have way more large forms than I did in my test,


Conner - after your comment I rechecked my graph and realised I made a mistake in representing the numbers. The graphs show the AVERAGE percentage of growth in each petri dish (four and five dishes cultured respectively in May and in October. 
When I wrote the percentage as numbers below the graph, I forgot to divide the sum with the number of dishes. That means, the average number of different forms is way lower than the numbers written (eg. average large forms after 30 days, October = *six percent*, not 30). I corrected the graph. (This mistake does not change the trend)


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## Crohn2357

irishgal - There is no "send" button for sending a message to Human Paratuberculosis Foundation on the contact page.

Edit: I see the "submit" button near the spam check feature (calculation question) now; but it is not visible if you don't put your mouse on it.


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## irishgal

Crohn2357 said:


> irishgal - There is no "send" button for sending a message to Human Paratuberculosis Foundation on the contact page.
> 
> Edit: I see the "submit" button near the spam check feature (calculation question) now; but it is not visible if you don't put your mouse on it.


Weird - I bet this is due to the latest WP update they just did that was huge. I see whta you mean. Looks ilke they switched the color on us for that form. I'll check into it and hopefully get it back to normal!


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## Crohn2357

I will probably start the Anti-MAP therapy in a month's time.

Questions: 

1)According to this page:





> From patients who have provided this information publicly, the most commonly used daily AMAT protocol is: 1000 mg. of clarithromycin, 300 mg. of Rifabutin, 2 mg. per kg. of clofazimine. These doses are split in half and taken throughout the day. Some doctors prefer to ramp up this therapy to minimize initial side effects, starting with lower doses and gradually increasing the strength to the full dose over time.


Does Dr. Borody use this protocol? 
2)I've read that Dr. Chamberlin uses different antibiotics, does anyone know why? Anyone know his protocol exactly?
3)Dr. Chamberlin states: 





> * I've heard some doctors start all of the medication at full strength on the first day, and some start with lower doses and gradually increase over time to the full dose. What are the benefits and drawbacks to each method?*
> I start my patients on the full dose on Day 1 to minimize the risk of bacterial resistance. This produces more common side effects, including nausea and feeling like you have the flu for a few weeks, but I believe this approach works well for the majority of patients. The doctors who choose to slowly increase the dosage over a period of weeks do so to minimize side effects for the patient. There may be some cases of patients who have recurrent obstructions or more severe side effects initially where I would consider a ramp up method, but no studies have been done to compare these methods side by side. Therefore, which method is superior is up to each practitioner’s opinion.


Which one is better, do you think? What do others (patients and physicians) think about this? Which method is more commonly used? Which method does Dr. Borody use these days?
4) Can I use 6-mp and the triple antibiotics (Clarithromycin, rifabutin, clofazimine) together? Do you know any patients who are using these together?
5)Which side effects are common? 
6)Does the altered taste perception and metallic taste in mouth (associated with clarithromycin)  get better in time?
7)I am prone to migraines and headaches in general, do you know if any of these antibiotics causes headaches (I know some antibiotics do), based on your or others' experiences?
8)I have read some patients use flagyl as the 4th antibiotic; how common and necessary is this? Do you know any other antibiotics that can be used as the 4th agent (ethambutol?, for example)?
9)Do you think prebiotic and probiotic supplementation is necessary? Do you have any specific recommendations with these?
10)Which antibiotics should be taken on empty stomach, which ones should be taken with food?
11)What is the generally accepted time-period to assess the efficacy of the treatment?


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## Connor

OleJ said:


> Conner - after your comment I rechecked my graph and realised I made a mistake in representing the numbers. The graphs show the AVERAGE percentage of growth in each petri dish (four and five dishes cultured respectively in May and in October.
> When I wrote the percentage as numbers below the graph, I forgot to divide the sum with the number of dishes. That means, the average number of different forms is way lower than the numbers written (eg. average large forms after 30 days, October = *six percent*, not 30). I corrected the graph. (This mistake does not change the trend)


I also got my blood done Otakaro. The conclusion that was drawn was that I was in active flare status or sub-optimal control. The presentation was identical to that of Crohn's patients, except I have received a dx of UC. 

Your numbers also match mine then, and you have CD. So this is all very fascinating. 

According to one theory I've read, adults who are infected with MAP tend to develop UC, not CD. Children exposed to MAP tend to develop CD.

My UC is severe. Every flare becomes fulminant, even with prednisone and hospitalization. I've refused surgery every time because I've known in my heart that an infection is somehow involved and I was only able to prove it with Otakaro two months ago!


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## irishgal

Crohn2357 - these are all great questions to ask on the Human Para Facebook private group or to discuss with your prescribing doc. AMAT is very situational, and a lot of the general info is given on Human Para, but each doc really needs to decide what's best for their own patient. I know Dr. Chamberlin will consult with other docs when requested, and I think Dr. Borody does too. The patient stories on Human Para may also give you some idea of what to expect in the way of side effects. Good luck!


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## Deleted member 431298

Crohn2357 said:


> I will probably start the Anti-MAP therapy in a month's time.
> 
> Questions:
> 
> 1)[...]


Very relevan questions! I hope that over time, as more of us manage to try AMAT, we will be able to have some of the answers in here.
Also thanks for sharing you plans. I am curious to hear if (and how) you managed to get your GP / GI on board? 
I tried to get my GI to read up on the core research pack at human para, but he never did and now he has quit. I am waiting for another one to start in January, and then I will ask if I too can try AMAT.


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## Crohn2357

OleJ said:


> Also thanks for sharing you plans. I am curious to hear if (and how) you managed to get your GP / GI on board?


I have inflammation and narrowing in my rectum and  I am considered non-responsive to conventional treatments. I am facing another resection surgery, which would leave me with a permanent stoma.

At this point, I did what I suggested in this post.

You can send a private message to irishgal or humanpara.org asking for a doctor who is open-minded about this treatment and is near you.

irishgal - In regards to the dosing of Rifabutin, I have found conflicting statements on Dr. Borody's treatment protocol from different sources. Here are some examples:

1) 





> *PARA: Can you describe your treatment protocol?
> Dr. Borody: *Our treatment consists of a combination of Clarithromycin, Rifabutin and Clofazimine. We commence treatment at a lower dose and raise to a higher dose after four weeks to try to avoid any profound side effects that can occur if we go to a high dose immediately. Following baseline studies of patients including blood workup, cross sectional ultrasound of small bowel (if small bowel is involved), inflammatory leucocyte bowel scan, colonoscopy with biopsies and photography, and small bowel X-ray if relevant - we then go on to commence the patient on the anti-MAP antibiotics. They are started with a dose of Rifabutin 150mg twice daily with food, combined with Clarithromycin 250mg twice daily and Clofazimine 50mg twice daily. Second weekly the patients undergo full blood count and liver function tests to monitor changes, especially in white cell count, neutrophil levels and liver function test elevations.
> 
> Generally speaking most patients have a minimal drop in white cell count, but many of these patients, being so ill, have highly elevated white cell count, so that this never reaches a leucopenia level. In three of twelve patients, when initially treated, we did reach leucopenia which was just below the level of normality, but we did not have to stop the medication in any of these because of our stepwise elevation of drugs. If this did occur, we planned to reduce the Rifabutin and Clarithromycin dosage down to 50% until the white cells recover. At four weeks the dose then goes up to 300mg of Rifabutin in the morning and 150mg at night and 250mg of Clarithromycin in the morning and 500mg at night. We use a high dose of Clarithromycin at night, to reduce the metallic taste which Clarithromycin can cause. For the next 24 months the patients are maintained on this treatment, progressively reducing and ceasing steroids and other Crohn's treatments.


http://www.crohns.org/treatment/borody.htm

2) 





> Borody's current protocol dosing is 1000mg clarithromycin, 600mg rifabutin (slowly ramped up from an initial 300mg over 3-4 months), and 150mg clofazimine (2mg/kg as Doug said).


https://anti-map.org/index.php/foru...-that-is-working-exceptionally-well?start=162 

3) This is from Humanpara.org. I understand that this does not specifically point out to Dr. Borody's protocol, but nevertheless, this suggests another different protocol.



> From patients who have provided this information publicly, the most commonly used daily AMAT protocol is: 1000 mg. of clarithromycin, 300 mg. of Rifabutin, 2 mg. per kg. of clofazimine. These doses are split in half and taken throughout the day. Some doctors prefer to ramp up this therapy to minimize initial side effects, starting with lower doses and gradually increasing the strength to the full dose over time.


https://humanpara.org/treatment-of-crohns-via-anti-map-therapy/

4) Again, from the same source above. This is the RHB-104 dosage, which was suggested by Dr. Borody If I am not mistaken. 


> RedHill gradually increases the dosage, with each capsule containing 95 mg clarithromycin, 45 mg Rifabutin, and 10 mg clofazimine. Eventually, the patient will take 5 capsules, twice a day for a total dosage of 950 mg. of clarithromycin, 450 mg. of Rifabutin, and 100 mg. of clofazimine.


Do you know what is his current protocol now? Dr. Borody is off on sick leave until the 1st of March, so I can't reach him.

I would appreciate your (and others', if anyone knows) input on this.


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## irishgal

Regarding rifabutin, there may have been some confusion early on about rifabutin vs. rifampin dosage. I clarified with Dr. Chamberlin recently, and he said it was generally 300 mg daily rifabutin, 600 mg daily of rifampin. Patients take one or the other. However, he also mentioned RedHill would sometimes use 450mg rifabutin, and they have done a lot of research on dosages. So definitely not 600mg rifabutin!


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## Deleted member 431298

Some thoughts on short-chain fatty acids (SCFA, such as acetate, propionate, and butyrate) and MAP. 

I realise this might seem a bit off the main topic of this thread, but on the other hand: What if SCFA's in some way inhibit MAP growth?

Science is currently focusing on the production of SCFA in the colon as a mechnism that may reduce inflammation. Interestingly
 one study by R Arrazuria et. al  found the butyrate-producing bacteria species _Anaerostipes_ to be negatively associated with MAP infection.

Not a whole lot of data I admit, but in order not to cherry pick, I did search for studies reporting no association between SCFA's and MAP, and found none. I thought I'd bring this up because there is so much focus on short-chain fatty acids and GI health in general:
Isolation of lactate-utilizing butyrate-producing bacteria from human feces [...] 
_Short-chain fatty acids [...] are formed by microbial fermentation, and influence the health and function of the host colon (Cummings, 1981; Mortensen & Clausen, 1996). In particular, butyrate is the preferred energy source for epithelial cells of colonic mucosa (Mortensen & Clausen, 1996; Hagueet al., 1997), stimulates cell proliferation (Sakata, 1987), and promotes mucus release from colonic mucosa (Shimotoyodomeet al., 2000). In addition, butyrate has been implicated in providing protection against colonic cancer and colitis (Whiteheadet al., 1986; Scheppachet al., 1992, 1998; Segainet al., 2000; Perrinet al., 2001; Ruemmeleet al., 2003). _

And this: _Bowel Wars: Hydrogen Sulfide vs. Butyrate_

The fuel for the bacteria producing SCFA's comes from Resistant Starches. This is interesting, as many of us try to _avoid_ starch altogether (SCD, paleo, GAPS). Maybe that strategy should be altered, so that we limit the amount of regular starch in the diet, but include Resistant Starches (along with fiber)...


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## Crohn2357

In Germany, some doctors have been using butyrate enemas (can't remember its clinical trial/trademark? name right now) to treat ulcerative colitis. 

The probiotic yeast S. Boulardii increases the amount of butyrate in the gut[1]. 

SCD restricts eating polysaccharides; but paleo has a wide spectrum ranging from very low carb (even ketogenic paleo) to high carb paleo... Paleo diet do not restrict eating polysaccharides, and most of the paleo websites I have seen endorse taking RS[2]. 
I think consuming RS is much more popular within the UC population than CD patients.

[1]:http://www.crohnsforum.com/showthread.php?p=884745#post884745
[2]:Sarah Ballantyne's warning is worth reading though: Resistant Starch: It’s Not All Sunshine and Roses


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## Deleted member 431298

_2]:Sarah Ballantyne's warning is worth reading though: Resistant Starch: It’s Not All Sunshine and Roses_
The main conclusion made by Sarah is that RS found in whole foods is beneficial, while the reducing RS foods may be why low-carbohydrate diets tend to alter the gut microbiome in unfavorable ways. It is only in one study where _isolated supplemenation_ of RS (which cannot be generalized into other types of RS) resulted in a slightly higher DNA adduct, which can reflect oxidative stress. My point being: I think the title _RS Not All Sunshine and Roses_ is too negative, and does not cover the topic very well.


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## Crohn2357

I guess the title reflects the writer's cautioning on the current "potato starch hype".


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## Crohn2357

Combining infliximab, anti-MAP and hyperbaric oxygen therapy for resistant fistulizing Crohn's disease



> *Lay abstract
> *
> Nine consecutive patients with Crohn's disease and fistulae were treated with a special combination of infliximab, numerous hyperbaric oxygen sessions and combined antibiotics including rifabutin, clofazimine and clarithromycin as the base antibiotic combination – called anti-Mycobacterium avium ss paratuberculosis (MAP) therapy. At between 6 weeks and 6 months all fistulae healed – included rectovaginal – so that the skin was dry and there was no discharge and no need to wear a pad. Their Crohn's symptoms of diarrhea, urgency and bleeding also resolved. Continuation with anti-MAP therapy alone maintained healing although one patient who ceased the anti-MAP therapy had a relapse.



This study was published in 2015 and it was posted in the Research subforum back then. I am posting it here so that more people can see it, especially for people who are dealing with fistulas. I think the study is remarkable.


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## Deleted member 431298

amazing results, thanks for posting this.


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## Crohn2357

You're welcome.


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## Crohn2357

Finding clofazimine:

From what I have read, some patients are finding and obtaining the clofazimine by using this website.


Clofazimine 50 mg Prices — Generic Version

Clofazimine 100 mg Prices — Generic Version


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## Connor

An update. I'm past the 6 week mark since starting AMAT. 

I have been having difficulties with the protocol. I've had an eye twitch for the past 3 weeks that won't go away no matter what I do, including magnesium. I've also been severely depressed and anxious, with bouts of fear and paranoia for no apparent reason. I thought it was maybe just the time of year but when I googled eye twitch and antibiotics, I was lead to many sites talking about the neurotoxicity of high dose clarithromycin that can cause these symptoms. 

The improvements  I mentioned earlier about my bowels were short lived. I'm back to bleeding and 5-6x daily BMs. They vary from 5-7 on the bristol scale. I've also started having upper GI pain that I've never had before in my life, including small intestine pain. I suspect that perhaps my bowel is being corroded by these drugs. Clarithro in particularly is *extremely* bitter. You have to take it with a full meal and even then it's hard on the body. 

I fear that the abx are causing damage to my body. Some of the reports I read said that people had these symptoms even a year after stopping. I'm beginning to doubt this course of action. Even if it does kill MAP, what's the point if it also causes brain damage? 

I'm taking 1000mg clarithro daily. I'm wondering if I should half that, even though AMAT research shows it to be ineffective at lower doses. The other problem is that sometimes the negative effects of clarithro don't kick in until weeks or months after you stop. While you're on them the body is in survival mode, putting everything it has into detoxing the abx... but once you stop it takes a rest and the true state of things is revealed.

Most MAP treatment protocols I've read say that improvements can start to be noticed as early as 1 month. For some people it's two months. It's weird how I had that brief period of 1 week with perfectly formed stool and no blood, to the point of constipation. Then it started to reverse again. Maybe that 1 week was the time of perfect equilibrium and now I am getting into imbalanced territory.

I am SO TIRED of playing guessing games with this disease. The only thing I can think to try is sending another blood sample to Otakaro to see if these 6 weeks have wiped out the majority of MAP. Though I don't see how that could be the case.

I also feel like whatever dysbiosis is being caused by the abx is a whole other level of body damage that's going to take me forever to heal. Last year I did a triple therapy for 10 days and it took about 2 months to start feeling normal. 

I'm scared right now.


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## Deleted member 431298

Conner, that's not what I had hoped for you at all. I am very sorry to hear you are getting no improvement and nasty side effects. Also, I am a bit puzzled as to why the MAP resources have no testimonies that resemble yours. Some ideas as to why:

A) - you are the only one having these exact reactions, or maybe some concurrent infection just happened to hit you, like C difficile or something (that would be unlikely, would it not?).

B) - other patients who got side effects like you describe pressed on, found relief, and never been bothered to mention the hardships in their reports. 

C) - those who get the serious side effects just quit to never look back and take the time to report what they experienced. 

D) - ?? some other reason ?? (any thoughts?)

From memory, the side effects that are reported are different, typically transient problems with eye inflammation (not eye twitching though), skin tone change. Anyone heard other reports of the symptoms Conner lists? (Irishgal?)

The neural symptoms sounds like something to take very seriously, and I totally get your considerations about quitting the abx. It seems like your situation calls for some expert guidence... 
I hope you will get better soon!


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## irishgal

Yeah Ole - These don't seem like the normal AMAT side effects that I've heard of in talking to patients. (Huge disclaimer - I'm not a doc!!) The hard part is MAP may not really be implicated in UC, though I know of one patient who did amazingly on AMAT and had true UC. For the majority of true UC cases (which aren't misdiagnosed as Crohn's colitis) AMAT seems to work less or not at all. 

Also, Connor seems to be extremely sensitive to antibiotics and meds. There are 10-15% of people per Dr. Chamberlin's anecdotal experience who just can't tolerate the meds. Some are allergic, and others just have a really hard time with them and have to stop. This is what's hard about not having a doc who is a MAP specialist to work with. There are so few docs who can adequately prescribe and adjust AMAT, and a lot of patients and docs are learning together.

There are other stories on forums and social media about AMAT not working for patients. None on HPF, but I've offered the option to a few patients who have interesting stories with this treatment, which ultimately failed. None have taken me up on my offer yet! I think Connor's story is either an anomaly specific to him, or maybe he has UC and the cause of his disease is not bacterial, or these meds aren't hitting at the specific bacteria. The fusobacterium varium research on UC is of interest to me, and it's a different regimen. 

Regardless, I hope and pray Connor finds something which will work for him!


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## Connor

There are 3 major variables here, actually 4.

1) Diet has been off lately, eating too much sugar (Christmas time)
2) Stopped prednisone just over a week ago.
3) Had an iron infusion 4 days ago.
4) My Entyvio dose is late by one week.

The anxiety/depression, I feel, is definitely abx related. I have not felt this way in a long time.


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## Deleted member 431298

I wish everyone reading and writing here a merry Christmas and a happy New Year. 
One of the better christmas presents is good news from the MAP vaccine development. They report the phase I trial was a success (test for safety on healthy individuals). The development now moves to phase IIa which is testing on Crohn's patients.

Keep it up, folks!

_‘The phase I trial was completed with no concerns over safety. As it was the first trial of this vaccine in people, a standard ‘3+3 dose escalation design’ was used to allow us to start with a very low dose for the first few volunteers and then gradually increase the dose once we were sure that there were no safety concerns. 

All doses were well tolerated, immunogenicity looks very promising, and the study is now being written up for publication.

We would like to thank the healthy volunteers who took part in this phase I study without whom it is wouldn’t be possible to develop important new therapies.’

Phase IIa, a further safety trial, this time in Crohn’s patients, remains likely to start in the first quarter of 2018, and we will provide further details about this once they become available. The set up period in clinical trials is often unpredictable and as such we are unable to give an exact start date for the phase IIa trial at the present time. Please note that recruitment has not yet started, so we therefore ask our supporters not to contact us or St Thomas’ Hospital about this. ..._


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## Deleted member 431298

There is an interesting comment by Dr. Greenstein and a colleague up on gastroendonews.com. The topic of the comment has been brought up previously in this thread but this new comment is well written and the argumentation rigorous, so I thought it was relevant to link to it:

To the Editor: More to the MAP Story

They reiterate the importance of acknowleding the anti-MAP effect of some of the usual CD drugs, in order to get valid results from past and on-going AMAT studies. Their primary concern is that the true effect of AMAT is hidden in studies, because the placebo-arm is inadvertently also recieving MAP-suppressing medicine:

_[...multiple medications used in the therapy of inflammatory bowel disease cause dose-dependent inhibition of MAP in culture. These include 5-aminosalicylic acid (5-ASA),10 methotrexate,8 6-mercaptopurine (6-MP),8,11,12 azathioprine,11 cyclosporine A,9 rapamycin,9 tacrolimus,9 the 1-hydroxypiperidine-2,6-dione component of thalidomide (Thalomid, Celgene)5 and the thioamides (methimazole and thiourea).6

These medications are called “anti-inflammatories” and “immune-suppressants.” These appellations may be wrong. We suggest that they are describing a secondary physiologic response. We posit that their primary mechanism of action is as anti-MAP antibiotics...]_


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## Connor

I came down an enterovirus this week that landed me in the hospital. They ran a CT scan as a precaution and it showed that I have extensive small bowel inflammation. My stool tests are negative for c. diff and other obvious pathogens. Based on my recent history, it's likely that the antibiotics have been ravaging my gut. I have been taking probiotics this whole time but they obviously aren't helping. 

On the advice of doctors and more importantly my own intuition, I've had to stop AMAT. My small bowel is in a lot of pain and my food absorption status is questionable. I've had to revert to taking morphine again. 

The preliminary assumption is that the antibiotics have been corrosive to my bowel and productive of new inflammation. Once the enterovirus hit, everything exploded. My CRP in the hospital was 120 despite no signs in my colon. For the first 4 weeks of AMAT I was also on prednisone. In the last 2 weeks all the pain and discomfort I was experiencing were probably the previously masked side effects of the abx coming to light once my pred taper was complete.

It's interesting that at the beginning of December I had perfect stools and it seemed like everything was normal, but it then turned to constipation and renewed inflammation. I still cannot explain this anomaly. 

The one thing I really need to say to the IBD / AMAT community at large that really is driving me crazy is that people need to STOP always calling symptoms "die off" when somebody complains about a set of symptoms. It's highly unlikely that you're having massive die off symptoms after a month of being on full dose AMAT. The majority of die off is going to happen in the initial stages as the active MAP + your gut flora are all dying. After that, "die off" events are more than likely something else, like your own native body tissue becoming inflamed, detox reactions from the antibiotics themselves, etc. When I told the ER doctors that I had been on Clarithromycin for 6 weeks they just shook their heads and said that it's a powerful antibiotic that is very harsh on the guts of most healthy people, let alone someone with IBD. I knew this going on, it's not news to me... but seeing the results in technicolour is another story! 

I am glad I gave this a try. I'm upset that I probably still have MAP but have no real way to deal with it now. I wasn't able to stay on AMAT long enough to look for evidence that my IBD was improving with it. What I should have originally done was waited 6+ months for my flare damage to heal before trying AMAT. It may also just be that I can't handle long-term antibiotics like this. 

The radiologist who examined my CT scan wrote in his report that I show Crohn's signs, but this should be re-assessed by a GI doctor. There are signs in the terminal ileum. The problem is that enteroviruses can also cause these signs so it's hard to distinguish. I will need follow up endoscopes. It's also possible that the antibiotics have been severely irritating to my gut but it was not possible to know due to simultaneously prednisone use. 

I will come back to give an update once I have more information. I am super depressed that this treatment avenue has turned out this way. I feel like the answers are all still unclear. If I do indeed have Crohn's then it means my original diagnosis was wrong or my UC has progressed to Crohn's, which would fit with the MAP picture. Unfortunately now that I have stopped AMAT, future resistance to AMAT antibiotics is likely. FMT is really my last treatment avenue... after that, I have nothing left to throw at my UC. I've done it all.


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## Deleted member 431298

I am truly sorry to hear that you got so ill. IBD is just such a F..&%"¤% piece of ..¤%"&&# disease. 
I probably mentioned this before, but Methotrexate (MTX) in a low dose (10-15mg/week) works well for me (with CD). It takes a month or maybe more for the full effect. Greenstein et al. found MTX to inhibit MAP in vitro. 
I hope you will stick around and share your thoughts with us. Your observations regarding the "die off" term are relevant.


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## SauceySciencey

irishgal said:


> Regarding rifabutin, there may have been some confusion early on about rifabutin vs. rifampin dosage. I clarified with Dr. Chamberlin recently, and he said it was generally 300 mg daily rifabutin, 600 mg daily of rifampin. Patients take one or the other. However, he also mentioned RedHill would sometimes use 450mg rifabutin, and they have done a lot of research on dosages. So definitely not 600mg rifabutin!


I was reading Dr Chamberlains Q&A, and he mentions the herxheimer reaction.

Typically, it's low level sepsis. 

That's fever, tachycardia, etc. It's the same "side effect" you get from vaccines (some people). Even non-vaccines will do it (obviously, since AMAT does it).

Crohn was trying to vaccinate people with anti-dysentery serum, and he found it only reduced symptoms, induced remission in people who had a reaction, much like the herxheimer. Other GIs of the time (Hurst, for example) then tried the same thing using silver/mercury/even horse serum. Same results. Only a response following the "serum shock"...

There is also the possibility that the antibiotic is efficiently killing alot of microbes, thus rendering the resulting broken up bacteria to be exposed and taken up through the intestinal wall and into the blood stream, and inducing "serum shock/herxheimer etc", which "resets" the immune system much in the same way Dr Chamberlain says.

It is more than possible that, in addition to hypothesising AMAT therapy works by targeting MAP, it also is equally possible, I suppose, that it is the mass wave of antibiotics killing any and all microbes and thus exposing the body to such a wave of antigenic diversity induces the herxheimer reaction which itself is the "culprit" for the clinical response. Whilst at this point all cards are on the table and each horse has a shot at winning, I lean towards this idea simply because it ties in across a spectrum of diseases (even cancer). But in the end, it's only the scientist in me that cares about that, the patient in me just wants something to work!


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## SauceySciencey

Connor said:


> I came down an enterovirus this week that landed me in the hospital. They ran a CT scan as a precaution and it showed that I have extensive small bowel inflammation. My stool tests are negative for c. diff and other obvious pathogens. Based on my recent history, it's likely that the antibiotics have been ravaging my gut. I have been taking probiotics this whole time but they obviously aren't helping.
> 
> On the advice of doctors and more importantly my own intuition, I've had to stop AMAT. My small bowel is in a lot of pain and my food absorption status is questionable. I've had to revert to taking morphine again.
> 
> The preliminary assumption is that the antibiotics have been corrosive to my bowel and productive of new inflammation. Once the enterovirus hit, everything exploded. My CRP in the hospital was 120 despite no signs in my colon. For the first 4 weeks of AMAT I was also on prednisone. In the last 2 weeks all the pain and discomfort I was experiencing were probably the previously masked side effects of the abx coming to light once my pred taper was complete.
> 
> It's interesting that at the beginning of December I had perfect stools and it seemed like everything was normal, but it then turned to constipation and renewed inflammation. I still cannot explain this anomaly.
> 
> The one thing I really need to say to the IBD / AMAT community at large that really is driving me crazy is that people need to STOP always calling symptoms "die off" when somebody complains about a set of symptoms. It's highly unlikely that you're having massive die off symptoms after a month of being on full dose AMAT. The majority of die off is going to happen in the initial stages as the active MAP + your gut flora are all dying. After that, "die off" events are more than likely something else, like your own native body tissue becoming inflamed, detox reactions from the antibiotics themselves, etc. When I told the ER doctors that I had been on Clarithromycin for 6 weeks they just shook their heads and said that it's a powerful antibiotic that is very harsh on the guts of most healthy people, let alone someone with IBD. I knew this going on, it's not news to me... but seeing the results in technicolour is another story!
> 
> I am glad I gave this a try. I'm upset that I probably still have MAP but have no real way to deal with it now. I wasn't able to stay on AMAT long enough to look for evidence that my IBD was improving with it. What I should have originally done was waited 6+ months for my flare damage to heal before trying AMAT. It may also just be that I can't handle long-term antibiotics like this.
> 
> The radiologist who examined my CT scan wrote in his report that I show Crohn's signs, but this should be re-assessed by a GI doctor. There are signs in the terminal ileum. The problem is that enteroviruses can also cause these signs so it's hard to distinguish. I will need follow up endoscopes. It's also possible that the antibiotics have been severely irritating to my gut but it was not possible to know due to simultaneously prednisone use.
> 
> I will come back to give an update once I have more information. I am super depressed that this treatment avenue has turned out this way. I feel like the answers are all still unclear. If I do indeed have Crohn's then it means my original diagnosis was wrong or my UC has progressed to Crohn's, which would fit with the MAP picture. Unfortunately now that I have stopped AMAT, future resistance to AMAT antibiotics is likely. FMT is really my last treatment avenue... after that, I have nothing left to throw at my UC. I've done it all.


Hi Connor

We haven't met but I was reading essentially the entirety of this message trail so by the end with this bad news it's like I'm feeling sorry for someone I know already! I'm really sorry things didn't work out for you like with others. I really hope you get a diagnosis soon and get a treatment plan in place. I remember being in that space of not knowing one way or another and also having to deal with pain etc. I hope you find, if not a way out of CD/UC land (we should find some musicians on this board, make a heavy metal PAIN band, and call them CD/UC (like AC/DC?)), then a way to get comfortable which is what all of us had to do at some point. There are some good and great people here who'll listen to you with more care than anyone in your life since we all know what your going through, and when we say "I understand" we really mean it!

Hope you feel better soon!


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## Connor

Now that I've stopped the antibiotics and have been doing intensive probiotics, my bowels have become a lot more regular. Solid stools, no blood, although I'm still going 4-5 times daily and there is pain from the recent rawness. I figure that will get better as time goes on. I was even able to start going back to the gym today. 

I have been wondering if maybe the 6 weeks of antibiotics cleared other things out that I'm not aware of. I'm also concerned that if my UC is MAP related, that the abx temporarily scaled back the numbers which is why I'm feeling so good. My research into mycobacterial infections has shown that most patients feel better within 1-3 months which tempts them to the stop the treatment because they think they're cured. Then the mycos come back and they're antibiotic resistant.

It's such a shame because underneath the antibiotics, it seems like I have a fairly healthy bowel now. It's possible that if I didn't have such a harsh reaction to the abx, that my current condition is what it would've been like while I was on them. 

I'm not really sure how to proceed going forward. Stopping the abx felt right, but my MAP treatment is incomplete. I flare with predictability once per year. I have confirmed mycos in my blood, but whether or not they are IBD related is hard to say. Otakaro does not identify them as MAP, just as mycos. 

So I don't really know what to do... that's where I'm at.


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## Crohn2357

About rifabutin dosage:
http://www.crohnsforum.com/showthread.php?p=997468#post997468


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## Deleted member 431298

Connor once again thanks for taking time to share your findings with us, although the outcome was not what one would hope for.

Also, thanks for linking to that thread Crohns2357. I was not aware this topic was so well discussed/covered already back in 2015.


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## Crohn2357

"AMA with Amy Hermon-Taylor, who fronts the Crohn's MAP Vaccine."


Addition: "IamA CEO of Qu Biologics developing a new investigational treatment for Crohn's disease. AMA!"


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## Connor

You're welcome OleJ. My plan is to see if my bowels achieve remission going forward. As I mentioned before, my UC is highly cyclical and refractory. I get a flare once per year like clockwork, but in between my bowels are very normal, so is my diet. So something is very amiss.

What I'm going to do is wait a couple months until the flare is well behind me, then I will re-test for mycobacteria at the Otakaro Lab. I want to see what my numbers look like under healthy conditions.

I also have the option of re-starting AMAT down the road. I might need a lower dose or a different combo of abx. All I know is that I don't want another life and death flare to strike again... I am so over it. 

For now I'm taking LDN 3.5 every night before bed, DHEA, and Entyvio once monthly.


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## Deleted member 431298

Hi all,
It's been a while and I wonder how you are all doing? 
I'm doing fine, trying to stay on the lowest possible MTX dose (7,5mg/week  + skipping some weeks). 
As an experiment I have started to boil the tap water before I drink it. Reports (not from my country though) have shown that MAP can contaminate drinking water and exist for up to a year outside the cattle it comes from. So why not give it a try.
I wish there were more studies done on the possible MAP contamination of drinking water.
Also, I met my new GI last week (the old one quit and moved to another hospital). I asked him about MAP, and he did not know anything about the current research. It is a real problem for us here that GI's are not updated. I mean, I would be way more comfortable if he'd said "yes, I know about it and from what I have gathered, and conferring with my colleagues, we conclude there is not enough evidence to treat MAP as a trigger of intestinal inflammation". But the reality is they don't know about even the Selby study, the Redhill trial, or JHT's vaccine trials. I would have thought it was common knowledge for a GI. 
The ones I have met so far have not even been interested.
Sighs.


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## 2522laura

Hi everyone. I just wondered if anyone in the UK had managed to get a Dr to agree to try the AMAT or LDN therapy? My Husband has severe crohns, had several operations, including a J pouch that was created around 18 years ago which is failing as its very scarred. Hes tried all biologics to no avail. We've been together for 9 years and he has not been in remission at all during this time. We saw his surgeon a couple of weeks ago who has suggested a permenant ileostomy but then went on to say he would have to take it above the internal pouch and leave the j pouch in situ because of the risks of taking it out (too many important nerves and blood vessels in the vacinity) but that there would be a 50/50 chance they would have to remove the j pouch anyway at a later date as they can become problematic (still making mucus) so in all he'd have a very high output stoma and the possability of serious issues with the surgery. 

As you can probably guess, at 38 years old and with a 5 year old child this is not really an option that he feels he can take given the quality of life it could leave him with.

His Crohns Consultant (Dr Parkes at Addenbrookes in Cambridge, UK) has never offered any alternative to the many biologics he has tried and I am wondering why, given the circumstances, he has not offered this. Surely he should be able to at least try it? 

I would love for my Husband to be able to transfer to St Thomas in London to see Dr Sanderson as he supports the MAP Vaccine research (Dr Parkes will not even entertain the idea) but I am not sure how we would go about getting a referal?

Any help would be most appreciated before we run out of time.

Thank you


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## Deleted member 431298

Hi Laura.
I am sorry to hear about your situation. In my opinion a good GI should either take an interest in the latest research and read up on it, or write a referral to another GI who is more knowledgeable in the field. 
If I were you, I would schedule a meeting with my GI and push for a referral. I actually got one from my GI a while back, but I have not used it.
The referral is actually pretty straightforward, you can fill out most yourselves, but your GI does need to fill in a few fields and sign.
Maybe an idea could be to print and give your GI the consensus document from the latest MAP conference, as well as (some of) the information on the humanpara.org page regarding til AMAT protocol.
I hope your husband will get better soon!


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## Crohn2357

Hi Laura.

You might want to contact with Human Paratuberculosis Foundation. 
You can also write to Anti-MAP facebook groups. 

You will probably get help from these sources, if you do write.


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## Nosebag

Hi Laura

I live in Ireland and wanted to try AMAT therapy so I paid to see Doctor Sanderson privately. I think it was around two hundred and fifty pound and that was two years ago. 
He gave me all the info and wrote a letter to my GI detailing the meds. My GI didn't really believe in this therapy either but he gave me the prescriptions. 
I did stay on infliximab and imuran with the rifabutin, clarithromycin and clofazamine as my disease was too severe at the time to risk removing them. Unfortunately it didn't work for me but maybe the other crohns meds hindered it's effectiveness or my disease was too active.


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## Deleted member 431298

Nosebag, thank you for your report. The way AMAT and other drugs interact is yet another unexplored field I guess. I for one have never come across any data. I guess another reason could be that your case of CD is not caused / sustained by MAP in the first place?


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## Crohn2357

Patient stories:

 Tried AMAT; it's working 

 My 1st day on AMAT and how I got my funded treatment


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## Crohn2357

NHS' recognition and permission for Anti-MAP therapy for treatment-refractory Crohn's patients who do not want to have surgery:






Date of Decision: April 2017
Date of Issue: May 2017


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## 2522laura

Thank you for sharing.

We've had a tough week, my Husband lost his mother last week and his Crohns has been relentless with bleeding and swelling - I guess due to the stress.

We have booked to see Professor Sanderson privately on 14th May, £300 for a half hour appointment but hoping it'll turn out to be a small price to pay for some kind of relief from his constant suffering.

We go on holiday on 21st May and he gets issues with the J-Pouch swelling during flights so really hoping it settles a bit before we go away


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## Crohn2357

2522laura said:


> Thank you for sharing.
> 
> We've had a tough week, my Husband lost his mother last week and his Crohns has been relentless with bleeding and swelling - I guess due to the stress.
> 
> We have booked to see Professor Sanderson privately on 14th May, £300 for a half hour appointment but hoping it'll turn out to be a small price to pay for some kind of relief from his constant suffering.
> 
> We go on holiday on 21st May and he gets issues with the J-Pouch swelling during flights so really hoping it settles a bit before we go away


You're welcome. I assume you read this thread?
 My 1st day on AMAT and how I got my funded treatment 

Things like meditation, cannabis, diets can be helpful with stress and gut inflammation. Let us know about your husband's appointment.


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## 2522laura

Yes I have thank you.

He has tried various CBD Oils, both with and without the THC but it didnt help. He has also been on oral pred since February which usually helps but hasnt touched it this time (he also followed this with pred suppositories as they were still on his prescription request but no improvement).

We still have the AMAT, LDN and Stelara to try, after that I guess it will have to be the stoma, though he is also seeing Guys & St Thomas colorectal team the day after the appointment with Professor Sanderson to see if they are of the same opinion surgery wise or if they think they will be able to strictureplasty the stricture above his J-Pouch, then at least we have done all we can to try and find a better solution to improving his life.


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## Crohn2357

I have read some patients use an anti-tnf biologic with anti-map therapy. I think this can increase the possibility of remission. Might be worth mentioning the doctor. 

As always, you can ask for other patients' experiences in the anti-map Facebook groups, they are helpful people. You can also contact Human Paratuberculosis Foundation to ask your questions, they may be able to get in contact with doctors who have knowledge/experience in anti-map therapy and ask your questions to them on your behalf.


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## Crohn2357

“Top-line results from the Phase III study with RHB-104 for Crohn’s disease are expected to be announced in approximately three months”

...

“RedHill will host an Analyst and Investor Webcast on RHB-104 for Crohn’s disease on Tuesday, May 15, 2018, at 8:00 a.m. EDT.

Members of RedHill’s executive team will be joined by key opinion leaders who will discuss RHB-104, the MAP US study, Crohn’s disease, the current treatment landscape and potential market. A question and answer session will be held following the presentations.

The conference call, including a slide presentation, will be broadcasted live and available for replay on the Company's website, http://ir.redhillbio.com/events, for 30 days. Please access the website at least 15 minutes ahead of the conference call to register, download, and install any necessary audio software.

Participants who wish to ask questions during the event can do so by telephone. To participate in the conference call, please dial one of the following numbers 5-10 minutes prior to the start of the call: United States: +1-800-263-0877; International: +1-646-828-8143; and Israel: +972-3-376-1315. The access code for the call is 1951893.”

https://www.redhillbio.com/RedHill/...id=1&LNGid=1&TMid=178&Fid=1384&Pid=0&Iid=7173


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## Crohn2357

Laura, how did your husband’s appointment with Dr. Sanderson go?


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## Deleted member 431298

very exiting news on the RHB-104 study. I am just now listening to a webcast presentation on their website. They claim that quote:

"Blinded blended (all patients) remission rate are superior to pre-specified assumptions"

My only worry is that they allow participents to be in treatment with 6-MP and Methotrexate. Given these drug's AMAT properties I fear the picture will be muddy (the effectiveness of RHB-104 will appear less  than it is in reality, because of the MAP suppression going on in the control arm).


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## 2522laura

It went really well thank you, amat is a possibility and he's also got him in with a good  dietician and on his nhs list for guys  hospital so will do his scopes etc and decide the best way forward but he said surgery was definitely not required.  Couldn't be happier that he may actually get his life back. He's a great guy and has given us hope when we felt like time had run out


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## Crohn2357

That’s great news Laura, I hope everything goes smoothly for you.


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## Crohn2357

> RedHill is conducting a first Phase III study of RHB-104 in Crohn’s disease (the MAP US study). The last patient enrolled in the study completed 26 weeks of treatment for primary endpoint evaluation in early May 2018, *and top-line results from the study are expected to be announced in the coming weeks.*





> If the MAP US study results are positive, RedHill will meet with key opinion leaders and the U.S. Food and Drug Administration (FDA) to present the data package and discuss the preferred path to potential approval.


https://globenewswire.com/news-rele...ne-Phase-III-Results-for-Crohn-s-Disease.html


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## Crohn2357

Finally, we will have a robust answer to the MAP problem, and possibly a new treatment option.


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## Deleted member 431298

Thanks for sharing. That is really exciting news. Let’s be sure to give the result a thorough review in this thread (or maybe a new one) and remember to present it to our GIs when it arrives  regardless of the conclusion!


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## Pangolin

Red Hill announced some results today.

"We are pleased to announce positive top-line results from the Phase III study of RHB-104 in #CrohnsDisease: https://t.co/6uqv2AedJq. Conference call to be held today at 8.30am EST: https://t.co/YRjQFcBXBg "

Moderately good results in a difficult to treat patient population. Red Hill's slide presentation has some more detailed info.

Here's the link to the presentation: http://ir.redhillbio.com/static-files/35b7a3f0-37d1-47bf-8a7d-7f8dce159732


----------



## irishgal

I think these are great results, and very comparable to all of the other conventional drug approvals out there for CD. One thing to keep in mind when comparing numbers. All of the biologics are allowed to skew their numbers by giving subjects a loading dose first, and then after 2 weeks, only enrolling the subjects who responded favorably initially. But clearly, that's not a true ITT analysis!

When someone told me this, I coukd 't believe it. So I actually read the two big Humira and Remi studies they used for approval (ex: CHARM). And what do you know - it's true. You have to dig in the appendices sometimes to get the raw data, but about 30-40% of the subjects who got the loading doses were weeded out after 2 weeks due to nonresponse! So I crunched the numbers again adding those people back in, and the remission rates were closer to 30%. So a 37% figure for RedHill is pretty darn good! 

Also, this was an add on study with other therapies as well, since the FDA was nervous about the placebo group being off everything for 26 weeks (understandably). They mentioned this in the webinar. But anecdotally from what I've heard from others, AMAT may work best when nothing else is used. I'm interested to see if there is a subpopulation of people on nothing who responded more favorably, and also to see what their secondary endpoint data shows in regard to MAP levels and endoscopic healing. 

Either way, this is a hallmark day for patients who can hopefully now look forward to a new therapy which works on a different theory. Hope this will spur further CD research in this area!


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## Pangolin

Irishgal: I think a lot of people (including investors who made the stock fall yesterday and today) were confused about the nature of this study.

1. The majority of participants have had Crohn's for 5+ years, are receiving standard treatment, yet still have high CDAI scores. These are well established and tricky Crohn's cases.

2. The placebo group isn't really just getting a placebo. They're also continuing on standard treatment eg remicade.

So getting a moderate response by adding on a treatment is pretty good in this group, and that's exactly what they found. 37% remission vs. 23% on placebo is a significant improvement and comparable to other widely used treatments.

My guess is that the results would be substantially better in an easier to treat group of patients.

People also looked at the 52 week remission numbers and were disappointed (I think it was 27% or 29% vs. 20% on placebo). It may not be a miracle drug for most patients, but I think they really succeeded in showing that it truly can help some people.


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## Crohn2357

Were the study participants (Crohn's patients) tested for MAP, does anyone know?

The antibiotic cocktail has a broad spectrum effect. Reduction in the gut microbiome population does result in healing and reduction in CDAI in Crohn's Disease; regardless of MAP.


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## eleanor_rigby

I think the disappointment for me was this avenue of research targeting this bacteria was kind of talked about as a possible cure avenue and these numbers do not reflect that. The remission rates of remicade and humira are not ideal. I guess I was hoping for much higher remission rates in this trial. I read somewhere that these results are similar to the findings when Crohn's patients are prescribed general antibiotics. Haven't investigated that to find out if there is any truth in it though.  
It is also frustrating they are using subjective outcomes, but irishgal said objective results are on their way.


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## Crohn2357

_RedHill Biopharma (NASDAQ:RDHL) says the market may be "confused" with the week 52 remission secondary endpoint from its Phase 3 clinical trial evaluating RHB-104 in Crohn's disease patients. Shares, initially up, sold off in apparent reaction to the endpoint which appeared to show only a modest separation from placebo.

The company says the endpoint measured "late induction of remission" and did not evaluate the preservation of remission over time. In other words, the endpoint meant to capture those patients who may have needed more than 26 weeks of therapy for initial induction of remission._

From: https://seekingalpha.com/news/33766...2-week-data-phase-3-study-rhbminus-104-crohns

_Regarding the standalone week 52 remission secondary endpoint, we believe there may have been some confusion. The standalone week 52 remission endpoint measures “late induction of remission” and does not evaluate preservation of remission over time. As such, this specific endpoint is neither a clinical nor a regulatory relevant endpoint. The standalone week 52 remission secondary endpoint was merely included by RedHill in the study to investigate whether certain individual patients might require more than 26 weeks of therapy for initial induction of remission. Accordingly, the analysis of standalone week 52 remission is an isolated exploratory outcome.

To emphasize, the clinically and regulatory relevant endpoint pertaining to week 52 is “maintenance of remission”, which by definition evaluates the maintenance (preservation) of remission from the induction of remission or response at an earlier time point to week 52. This “maintenance of remission” endpoint, in conjunction with a separate early “induction of remission” endpoint, has served as the basis for approval of current standard-of-care therapies for Crohn’s disease. In this endpoint, maintenance of remission from the induction of remission at week 16 to week 52, RHB-104 was twice as effective as placebo with high statistical significance (25% vs. 12%, RHB-104 and placebo, respectively, p= 0.007)._ 

From: https://seekingalpha.com/pr/1723235...top-line-results-phase-iii-study-rhbminus-104


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## Crohn2357

Crohn2357 said:


> Were the study participants (Crohn's patients) tested for MAP, does anyone know?
> 
> The antibiotic cocktail has a broad spectrum effect. Reduction in the gut microbiome population does result in healing and reduction in CDAI in Crohn's Disease; regardless of MAP.


Were all/majority of the study participants tested for MAP before or during enrollment, and which testing procedure was used (the old ones or the newly developed ones)? How many of them were tested positive for MAP? Why not all of them were tested positive for MAP, if MAP is the causative agent? How many of the MAP positive subjects responded to the anti-MAP treatment, and how well did they respond?

What do these data say to us for the age-old MAP problem, and also the possibility of a cure for Crohn's?

Reduction in the gut microbiome population does result in mucosal healing and reduction in CDAI; regardless of MAP. So, even if MAP is completely irrelevant, a positive effect from the antibiotics is expected.

I think the distinction between the reduction of commensal bacteria (bacterial burden) or "anti-map effect" should be made when analyzing the trial data and the effectiveness of the antibiotics.

I will wait for the anti-MAP vaccine trials for a better answer to the MAP problem.


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## eleanor_rigby

Crohn2357 said:


> Were all/majority of the study participants tested for MAP before or during enrollment, and which testing procedure was used (the old ones or the newly developed ones)? How many of them were tested positive for MAP? Why not all of them were tested positive for MAP, if MAP is the causative agent? How many of the MAP positive subjects responded to the anti-MAP treatment, and how well did they respond?
> 
> What do these data say to us for the age-old MAP problem, and also the possibility of a cure for Crohn's?
> 
> Reduction in the gut microbiome population does result in mucosal healing and reduction in CDAI; regardless of MAP. So, even if MAP is completely irrelevant, a positive effect from the antibiotics is expected.
> 
> I think the distinction between the reduction of commensal bacteria (bacterial burden) or "anti-map effect" should be made when analyzing the trial data and the effectiveness of the antibiotics.
> 
> I will wait for the anti-MAP vaccine trials for a better answer to the MAP problem.


Agree with all of this.


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## irishgal

I don't necessarily agree with the above and here's why:

First, RedHill did test for MAP levels throughout, and they said that data is still to be released. That will answer a lot of your above questions in regard to MAP in this study. Which the validity of which has to be balanced against their MAP test, and they will hopefully release details of their methodology in a peer reviewed journal. Those results will help move MAP science forward I think.

Secondly, I don't think anyone but the MAP vaccine folks term any of this a cure. I look at the RedHill trial as another weapon in the arsenal against CD. It may be MAP only affects a subpopulation of CD patients, and for those patients who are miracle responders, long term healing could approach a “functional cure”, defined as being off all meds for a long period of time without any relapse of CD symptoms. There are some who have achieved this via Prof. Borody's center. They are not the majority, but there are enough of them that it's a possibility for some. But we need more long term data to determine any of this. 

Lastly, I don't think you can make the assumption that overall reduction in the microbiome will help CD patients, and therefore antibiotics work generically and not specifically on MAP. This has been one of the huge questions in MAP science and it remains unanswered. However, these antibiotics specifically target mycobacteria. They may work on some others, but it is not true that all antibiotics work to reduce all bacteria. Antibiotics have a specific target, and these are ideal for mycobacteria. Again, we need data for this, and I'm hopeful that this first study will lead to more funding for MAP research so we can answer these data gaps. From a drug company's perspective and on some level to the patient, it doesn't matter WHY the treatment works, only that it DOES. Sure it would be nice to know the why, especially in the case of MAP, but in the meantime, RedHill will hopefully get this therapy FDA approved and then anyone can get it easily! I see this study as a huge win.

I know you are waiting for the MAP vaccine, as are many others, but there have been no peer reviewed papers on this in probably around a decade. This is not the way standard medical research is done. I'm not sure where this project is going and I have doubts about the science of it. I wish them the best, but I'm not counting on it as a treatment option in the next 10 years. RedHill released results now and has given a very detailed path forward, and that's something I CAN count on.


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## eleanor_rigby

Hey irishgal. I agree with what you are saying. I think the thing is with the MAP theory there is a lot of buzz around it because it held/holds the potential to explain the cause of Crohn's in some/all. There aren't really many other avenues being explored right now as the underlying cause of Crohn's. It really would be amazing if the cause was due to a bug just like helicobacter pylori. If they knew the cause to be a bug like that, then a cure would be imminent. We all want to get off immune suppressing drugs.

I see that you say that no one really ever viewed this as a cure except the MAP vaccine folks, and that is fair enough. However, I guess I was hoping for more people to have the "functional cure" you speak of in the trial. I was hoping for numbers more like 77% in remission as opposed to 37%. As I said, the numbers in remission on remicade / humira etc are not ideal. I think we all want meds that help a majority of people, not less than half of people.

It's interesting the point you make about the MAP vaccine - with there being no peer reviewed papers in around a decade. I do find that concerning. It is excellent that Redhill are paving the way for more studies and hopefully approval for this drug. The more drug options we have, the better. I have my fingers crossed that endoscopic data strengthens their findings and does not weaken them.


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## Scipio

I find the result both encouraging and disappointing at the same time - for most of the same reasons mentioned in the discussion above.  It will be good to possibly have another tool to help manage Crohn's, but it's miles from being the big cure that MAP true believers have been expecting.  

I look forward to eventual FDA approval and having one more option to consider when and if the more effective medications stop working or were not enough in the first place.


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## Crohn2357

Scipio said:


> I find the result both encouraging and disappointing at the same time - for most of the same reasons mentioned in the discussion above.  It will be good to possibly have another tool to help manage Crohn's, but it's miles from being the big cure that MAP true believers have been expecting.
> 
> I look forward to eventual FDA approval and having one more option to consider when and if the more effective medications stop working or were not enough in the first place.


I agree.


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## irishgal

For me personally, I tend to hope for the best, but plan for the worst in all areas of life. True CD patient, right! MAP seems like a tough bug to crack, so I was never hoping for huge numbers or a cure out of this. With some tweaking or with another to be created combo therapy, maybe. But these results are about on par with all of the other approved CD drugs. AMAT has provided me nearly 4 years of no CD, and I'm currently on 2 meds, full strength, every other week to hopefully keep whatever I have left in dormancy. I'll take what I can get to beat this horrible disease! I got before and after MAP tests though from Otakaro, so I know for sure my issue was mycobacteria. Maybe others have other issues. 

There is currently a debate about what percentage of CD patients have MAP as their primary issue, and that number ranges from about a third, to 100%. The current data, which is hard to consider fully reliable, tests around 30-40% I think. And if you see the RedHill results showed around that number too. Unlike the biologics, they didn't “prime” people for a few weeks with the drug and then only take the ones that responded. Their figures at the 16 week mark were good, and the subset of people who responded at 16 weeks had significantly increased remission rates at 52 weeks. 

Also, and this is just a hunch of mine, but I really think AMAT works best when tried 1) as a first line therapy and 2) without any other meds. This was not the study run by RedHill for a bunch of reasons, but they talked about doing this type of study eventually. I think the biologics create dormant, resistant MAP, and that could explain some of these results. I'd be curious to see results of this used first line.

All of this to me adds up to that some people respond really well to AMAT, and some just don't. Whether it is only MAP and those are resistant strains, or whether MAP is only a subset of CD patients remains to be seen. Very excited about their secondary data endpoints, like the MAP levels. I have a feeling this first study will spawn many more and we'll start working on a complete picture of MAP's role in CD. Funding has been a serious issue and has held the science back for a very long time.


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## Scipio

One interesting line of research I would like to see tried would be combo therapy.  Treat treatment-naïve patients with the Redhill drug regimen or something similar in combination with say azathioprine or infliximab, or usetekinumab - to battle the disease at the front end and the back end both at the same time.


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## Kas8173

To those of you who have had AMAT, how did you get it? I would be particularly interested if anyone from the UK has managed to get it.

I have had Crohn's for around a year now, it is active at the moment but not severely. Although the odds are it will get worse at some point in the future in my life.

I have asked several consultants about having AMAT, but their response has been along the lines of: We only give this in severe cases. You haven't tried Methotrexate, Azathioprine, Anti-TNF therapy yet, and we'd only consider AMAT if you had tried those and didn't respond.

For someone who believes that MAP is the cause of Crohn's, this logic seems backwards. If someone had a TB infection that wasn't severe (like latent TB) the doctors wouldn't say, "We're not going to treat your TB infection with antibiotics yet because it's not severe, we're just going to give you drugs that mask the symptoms for now". 
What you would want to do is kill the infection as soon as possible with all you've got.

My mind is made up. I have read enough studies to convince me that AMAT is more effective, and also has fewer side effects than other treatments like Mtx, Aza, Anti-TNF and steroids.

Can anyone put me in contact with a doctor in the UK who we know is willing to try this? Or give me any advice on how I would look for one?

Edit: Dr. Sanderson of Guy's hospital was mentioned in a previous post. I would be really grateful if I could have some more info about him.


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## irishgal

Dr. Sanderson may be your best bet. He sees patients privately at the Shard Building in London. I've heard he is a very good doc.


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## Kas8173

I have emailed Dr. Sanderson. I would happily pay to see him privately after the many positive testaments I have read on this forum and others.
Let's hope he has the time to reply.


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## Crohn2357

A discussion on the RedHill's recent announcement about RHB-104:

https://www.healingwell.com/community/default.aspx?f=38&m=4044862


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## Kas8173

Do we know of anyone having anti-MAP therapy at the same time as a biologic or immunomodulator? (Infliximab, Adalimumab or Azathioprine)?

I remember something that Dr. Borody mentioned in one of his interviews was that it would be interesting to see the results if this was the case. Since biologics and Azathioprine trigger apoptosis (self destruction) of macrophages where the MAP is hiding, it would seem logical that it would make the antibiotics more effective and faster to induce a response.

Although an increased chance of liver toxicity would be a concern.


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## Crohn2357

Another "I started Anti-MAP" thread


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## Xavke91

Hello everyone,

I have started the anti-map treatment 2 weeks ago. I am on 200mg Rifampicin daily, 100mg Clofazimine and 750mg Clarythromicin. 

I would like to ask people who tried or are currently on the treatment how it went the first couple of weeks / months. When can I start expecting results? I feel terrible at the moment (no energy, headaches, pressure behind my eyes,...), did you experience any side-effects and did they go away? If yes after how long? 

I was joyful when I read the results of the Redhill study. However, people in the study only noticed effects after 4 months and achieved remission in 6 months. Will it be the same for us? I think the participants were on lower dosages. 


kind regards,

Xavier


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## irishgal

Hi Xavier - my case was fast in that I started to see improvement by 2 weeks. Still kind if felt horrible (like what you are describing) but I was on higher doses right from the start. It sounds like you are having the typical flu like symptoms. The only thing you may want to get checked out is the eye pressure. Have not heard of that before. When I went through this period, my doc told me to baby myself, take it easy, lay on the couch and watch movies, eat well, and not expect too much. He said symptoms will slowly start melting away, and that was a very accurate description. I found it helpful to keep a journal about how I felt each day, so each week I could track if I was getting better.


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## Xavke91

Thanks for your reply Irishgal. How long did this off-period last for you and what were your negative side-effects? When I look in the mirror now I see a zombie... Also, could I ask what the first symptoms of improvement were that you experienced?

My case is quite special, I'm currently on Vedoluzimab for almost a year now. On paper, my inflamation values are very good. So my doctor keeps telling me I'm in remission. However, none of the Crohn's side effects went away. I'm chronically fatigued, can't gain a single kilo (I'm 7kg's under weight) and my diarrhea never went away. So hoping the improvement from the Anti Map treatment will include energy, weightgain and less diarrhea. 

Thank you for the tip on the journal. Will do this!


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## irishgal

Yes - zombie is a good way to describe it initially. Exhausted, running back and forth to the bathroom, horrible nausea, stomach pain, fever, chills, lack of wanting to do anything other than curl up in a down comforter and hide in bed (it was winter when I started!) After a few weeks I noticed my skin form of CD starting to heal rapidly. That was amazing, since the skin part was hugely painful and almost worse than the GI symptoms, which I was used to after 25 years.

After the nausea went away, I got intensely hungry and ate a ridiculous amount. By 6 weeks I had gained 10 pounds. I also had night sweats for months, which I think was my body's way of getting rid of toxins. I think the things you want to achieve are possible if the therapy works, so just take it easy. It may take a few months. The D was the last symptom of mine to resolve, and while the trips to the bathroom were reduced over time, to get the D to fully go away took about 9 months I recall. 

And my doc would soemtimes tell me I was doing OK due to low-ish inflammatory markers, but I still felt terrible. That was addressed a little at the conference this weekend. The markers of healing and inflammation don't always correspond exactly to how the patient feels, which is interesting. I'd also recommend trying to do everything you can to help your body recover, like getting enough sleep, doing some exercise, eating well and avoiding trigger foods and things like sugar and fried or processed junk food. That seemed to help me a lot initially. Ginger and peppermint tea were also very helpful. Keep in touch with your doc if you feel like there's something really horrible or out of the ordinary going on as well!


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## Xavke91

irishgal said:


> Yes - zombie is a good way to describe it initially. Exhausted, running back and forth to the bathroom, horrible nausea, stomach pain, fever, chills, lack of wanting to do anything other than curl up in a down comforter and hide in bed (it was winter when I started!) After a few weeks I noticed my skin form of CD starting to heal rapidly. That was amazing, since the skin part was hugely painful and almost worse than the GI symptoms, which I was used to after 25 years.
> 
> After the nausea went away, I got intensely hungry and ate a ridiculous amount. By 6 weeks I had gained 10 pounds. I also had night sweats for months, which I think was my body's way of getting rid of toxins. I think the things you want to achieve are possible if the therapy works, so just take it easy. It may take a few months. The D was the last symptom of mine to resolve, and while the trips to the bathroom were reduced over time, to get the D to fully go away took about 9 months I recall.
> 
> And my doc would soemtimes tell me I was doing OK due to low-ish inflammatory markers, but I still felt terrible. That was addressed a little at the conference this weekend. The markers of healing and inflammation don't always correspond exactly to how the patient feels, which is interesting. I'd also recommend trying to do everything you can to help your body recover, like getting enough sleep, doing some exercise, eating well and avoiding trigger foods and things like sugar and fried or processed junk food. That seemed to help me a lot initially. Ginger and peppermint tea were also very helpful. Keep in touch with your doc if you feel like there's something really horrible or out of the ordinary going on as well!


Thank you so much for your detailed response. I guess all I can do is wait and see what happens. How long did it take for your tiredness to go away? The reason I'm trying this is to get rid of it, but now that it became even worse I'm hoping it will fade away. I don't have fever, chills, more diarrhea, nausea,... however.

Oh and I see that you take (or took) LDN. Would you recommend this?


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## irishgal

I can't recall exactly on the exhaustion when it started going away. Maybe a few months? I have little kids though, so constantly live in a state of semi-exhaustion. I have a lot more energy now that I'm better though, so the exhaustion from the CD has probably resolved now, but the exhaustion from kids, work, not enough sleep and daily life is probably self imposed. 

And yes - I started LDN arund 6 months into treatment when Levo failed. I was prett much better by then, so it's hard to know if it's doing anything. My integrative doc recommended it to help my immune system. So far I'm well, so not rocking the boat!


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## Crohn2357

Xavke91, I have tried LDN in the past. My disease was very severe and nonresponsive to the immunosuppressives, biologics, and the combination therapies. The LDN significantly lowered my CRP count (more than any other drug), but it didn't give me remission. My symptoms were a little better; but not much change. I took 4.5 mg right from the beginning, and took it for about four months, if I remember correctly. 

As for recommendation, If you make a thorough research about it yourself, and think it would be good for you; then why not? It seemed to me safe back then. I don't know how the anti-map and LDN interact, maybe look into "Drug Interaction Checker" links for naltrexone and the antibiotics used for the anti-map therapy. Ask about it in the anti-map facebook groups, and the other online forums.


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## Xavke91

irishgal said:


> I can't recall exactly on the exhaustion when it started going away. Maybe a few months? I have little kids though, so constantly live in a state of semi-exhaustion. I have a lot more energy now that I'm better though, so the exhaustion from the CD has probably resolved now, but the exhaustion from kids, work, not enough sleep and daily life is probably self imposed.
> 
> And yes - I started LDN arund 6 months into treatment when Levo failed. I was prett much better by then, so it's hard to know if it's doing anything. My integrative doc recommended it to help my immune system. So far I'm well, so not rocking the boat!


Hi Irishgal, I have a quick question. My doctor wants to prescribe me steroids for inflammation that is going up again. Is it safe to take corticosteroids with amat? I read in a pamflet online that amat and steroids can be prescribed together. They want to give me Budesonide, but when I look online I see written that clarythromicin and Budesonide should be avoided? Do you know anything more? Thank you!


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## Xavke91

Crohn2357 said:


> Xavke91, I have tried LDN in the past. My disease was very severe and nonresponsive to the immunosuppressives, biologics, and the combination therapies. The LDN significantly lowered my CRP count (more than any other drug), but it didn't give me remission. My symptoms were a little better; but not much change. I took 4.5 mg right from the beginning, and took it for about four months, if I remember correctly.
> 
> As for recommendation, If you make a thorough research about it yourself, and think it would be good for you; then why not? It seemed to me safe back then. I don't know how the anti-map and LDN interact, maybe look into "Drug Interaction Checker" links for naltrexone and the antibiotics used for the anti-map therapy. Ask about it in the anti-map facebook groups, and the other online forums.


Which are the anti-map facebook groups? Thanks!


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## Kas8173

The risk with taking clarithromycin and budesonide together is that the clarithromycin may inhibit the breakdown of the budesonide and allow it to escape the first pass metabolism and become more of a systemic steroid than a localised one.
In short it may mean that the budesonide acts more like prednisone and has effects on the whole body rather than just the gut like it usually does.
If you take the budesonide first thing in the morning and then the clarithromycin at least 3-4 hours afterwards you will lessen the risk as most of the budesonide should have been processed by then anyway.
Some other anti-MAP antibiotics that have this same effect include rifampin and isoniazid.
I have taken this combination together myself and been fine. There is the potential for many interactions with anti-map antibiotics, the drugs.com interaction checker is a good resource.

But as always, don't rely solely on my advice or that of the interaction checker, always ask your doctor if you are unsure.


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## Crohn2357

Xavke91 said:


> Which are the anti-map facebook groups? Thanks!


I don't visit them, but I know there are anti-map groups on facebook. Just write "anti map" and "anti map Crohn's" on the search of facebook, you will probably see them.


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## Crohn2357

2018 MAP Conference Presentations



irishgal said:


> Videos from the conference are up. We're still working on a few of them - our audio wasn't great at the facility, but at least half are viewable now: https://humanpara.org/2018-map-conference-presentations/


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## irishgal

Xavke91 said:


> Hi Irishgal, I have a quick question. My doctor wants to prescribe me steroids for inflammation that is going up again. Is it safe to take corticosteroids with amat? I read in a pamflet online that amat and steroids can be prescribed together. They want to give me Budesonide, but when I look online I see written that clarythromicin and Budesonide should be avoided? Do you know anything more? Thank you!


Not totally sure on the interactoins. Not a doc, but sounds like there may be some issues from the other posts. I do know people taper off of steroids by introducing AMAT, but not sure which form of steroids they were talking about. Maybe just straight pred. When in doubt, I'd always ask the doc!


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## Crohn2357

RedHill BioPharma takes an antibiotic approach to Crohn's disease


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## Crohn2357

Letter to NICE regarding Crohn's Disease management update CG152



> Dear Sir / Madam,
> 
> As a group of patients with Crohn’s Disease, close family members and friends or doctors with an interest in Inflammatory Bowel Disease, we would like to request that your current review of the guidelines for post-surgical Crohn’s disease management include discussion of the option of anti-MAP antibiotic therapy (AMAT) for the treatment of Crohn’s. AMAT is a treatment combining the antibiotics Clarithromycin, Rifabutin and Clofazimine to target Mycobacterium avium subspecies paratuberculosis (MAP). The rationale for this treatment is based on increasing evidence supporting the hypothesis that Crohn’s disease is caused by MAP in susceptible patients.
> 
> In particular, we would request that the panel review the recent data from the phase III randomised controlled trial ‘Efficacy and Safety of Anti-MAP Therapy in Adult Crohn's Disease’ (MAPUS) led by Redhill Biopharma (https://tinyurl.com/RedhillRHB104)  and consider whether AMAT should be included as an additional treatment option in the updated guidelines. These recent trial data suggest both safety and efficacy of this treatment over standard care including corticosteroids, immunosuppressants, oral 5-ASA compounds and biologics (infliximab or adalimumab). Of note, AMAT does not carry the rare but life-threatening risks associated with biologics (e.g. lymphoma) nor the risks associated with long-term immunosuppression. At a cost of £4660 for a 12-month course, the treatment compares favourably to current therapies in terms of cost-effectiveness.
> 
> Given these data are in the public domain, it seems likely that many patients will seek information and guidance on this new treatment option. It is therefore important that national recommendations provide guidance for doctors making difficult decisions together with patients who may have exhausted all other treatment options.
> 
> We thank you in advance for your consideration and look forward to your response.


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## Crohn2357

https://www.sciencedirect.com/science/article/pii/S1590865807000138

Anti-mycobacterial therapy in Crohn's disease heals mucosa with longitudinal scars
T.J.BorodyS.BilkeyA.R.WettsteinS.LeisG.PangS.Tye

Abstract
Background
A possible causative link between Crohn's disease and Mycobacterium avium ss paratuberculosis has been suggested.

Aim
To report unique scarring in Crohn's disease patients treated with anti-Mycobacterium avium ss paratuberculosis therapy.

Patients
A retrospective review of 52 patients with severe Crohn's disease was conducted. Thirty-nine patients who had at least one follow-up colonoscopy during treatment were included.

Methods
Patients received rifabutin (up to 600 mg/day), clofazimine (up to 100 mg/day) and clarithromycin (up to 1 g/day) – anti-Mycobacterium avium ss paratuberculosis therapy – for 6 months to 9 years. Ramp-up dosing was used. Colonoscopies and histological analyses monitored progress.

Results
Twenty-two patients (56.4%, 22/39) healed with unusual scarring, which appeared as branched, ribbon-like, elevated lines. In 2/6 patients (33.3%) who had >3 years of treatment after scarring occurred, scars receded, becoming imperceptible as full healing occurred. Histologically, a marked reduction in inflammation occurred in 15/39 patients (38.5%). Of these, 6/15 patients (40%) displayed restoration of normal mucosa. Longitudinal scarring occurred in 12/15 patients (80%) with improved histology.

Conclusions
The presence of scarring fading to normal mucosa on anti-MAP therapy implies a more profound healing not seen with standard anti-inflammatory and immunosuppressant drugs. Longitudinal scarring and consequent healing with normal histology should become a standard treatment goal for Crohn's disease.


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## Crohn2357

KarlB said:


> I forgot about this post for a while but I am doing very well now.
> Within a week of starting the infliximab all of my symptoms went completely away and I started putting weight back on. I was previously underweight.
> My calprotectin went from being around 1100 to low 20s within 3 weeks.
> I have now been in total remission for around 2.5 months and have put on around 5kg in weight.
> This is quite significant considering that a few months ago, in the words of my consultant, I had severe pan-enteric crohn's disease with lesions in the stomach, duodenum, ileum, terminal ileum and right side of the colon.
> I will never know whether I would have had such a good response without the anti-map but my consultant says that my response has been faster and better than you would usually see with infliximab alone.
> My plan is to continue the infliximab maintenance indefinitely or until I lose response to it. I plan to continue the azathioprine at full dose, and if I reach 6 months of remission, go down to half the dose of azathioprine since there is some research which suggests full dose is no more effective than half dose after 6 months of remission in combination therapy.
> I plan to continue the anti-map for 1-2 years depending on whether or not I stay in remission.


	Another "I started Anti-MAP" thread


----------



## Nosebag

Hi

I am currently on Anti map therapy the last 4 weeks 150mg of rifabutin twice daily, 500mg clarithromycin once daily and 100mg of clofazamine daily. My weight is around 120lb or 54kg. Is the dosage of my medication correct for my weight? 
I still take stelara every 4 weeks also. I don't know if the anti map is working as of yet or if I am on the correct dose.
If anyone knows the answer I would be grateful.


----------



## Kas8173

Hi Nosebag. A good reference for the drugs and dosages are here: https://humanpara.org/for-clinicians-chamberlin-amat-protocol/
Your dosages are correct apart from the clarithromycin which should be 500mg twice daily instead of once.
How did you get the Anti-map?
Hopefully you should see improvements in the next few weeks.
Are you on an immunomodulator as well such as methotrexate or azathioprine/6MP?
Anti-Map with ustekinumab may be a good combination.


----------



## Nosebag

Kas8173 said:


> Hi Nosebag. A good reference for the drugs and dosages are here: https://humanpara.org/for-clinicians-chamberlin-amat-protocol/
> Your dosages are correct apart from the clarithromycin which should be 500mg twice daily instead of once.
> How did you get the Anti-map?
> Hopefully you should see improvements in the next few weeks.
> Are you on an immunomodulator as well such as methotrexate or azathioprine/6MP?
> Anti-Map with ustekinumab may be a good combination.


Hi Kas8173

I tried it a few years ago and it didn't work. Doctor Jeremy Sanderson prescribed my dose and gave me information to give to my GI.That was the dose he prescribed at the time so I thought it was based on my weight. I have high liver counts previously so I hope they will allow me up the dosage.
I have taken Imuran and different biologics previously and they failed. My large bowel is diverted and I have an ileostomy but crohns has returned in both areas.
Thanks for your help.


----------



## scafo88

anyone with a child on anti map?


----------



## Crohn2357

Scafo88, I am adding your first post here, so that more people can see it. Maybe someone will give you a good information.



scafo88 said:


> Hi All -
> 
> My son (10) started anti-map therapy a week ago. I would love to hear any other parents/folks experience. A little about my son. He was dx at 6 with UC then it changed to Crohns and now we sit at Indeterminate colitis. I sent his blood off to New Zealand to culture for MAP. It came back highly suggestive of MAP. My son previously failed, steriods, 6mp and remicade.
> 
> He has always been a bleeder and that has been one of our biggest issues. He doesn't have small intestine involvement (thank goodness) but does have joint pain, uclers and developed seizures which we had to medicate for. Please don't go into the neuro-toxicity of anti map or other meds because I am well aware of all of it.
> 
> I want to know how long it took to see bleeding stop on Antimap? My son has been super weepy which is not like him and I attribute that to the therapy as well. Anything you can offer would be greatly appreciated!
> 
> Thank you


I am not a medical doctor, nor licenced to give medical advice, I am a Crohn's patient like others here, and reading what you wrote about your son, if I were in your shoes, I would definitely consider the anti-map therapy. It seems well justified in his case: The disease looks severe (or at least problematic); lab results for MAP came back "highly suggestive"; his disease has not responded to the conventional immunosuppressant treatments; he is young and still at the developmental age and needs good nutrition, absorption, and his inflammation to be down as soon as possible; he has seizures (I have read MAP might also cause neurological disorders) which might become better with the antibiotics.

Regarding how long the anti-map therapy takes to work, I think it depends on the person. I assume, since he is a child and his lab results came back high, he might have a quick response (if he is to respond, that is).

In the first post of this support group, I provided many useful links, some of which contain useful and practical information about this therapy while the others are links to other support groups (facebook groups, and a forum for patients who use/consider to use the anti-map therapy). I would consider being a member to them and asking my questions in those pages too. You can also contact Human Paratuberculosis Foundation by clicking this link to ask your questions. They might help you.

If you decide to start him the therapy, definitely do this under a doctor's supervision. If you describe your situation to the Human Paratuberculosis Foundation and ask for a doctor's name who is near you and is willing to use this therapy, they might provide you that information. I believe irishgal might also provide you this information, you can send a private message to her through this link. She has first hand experience with the anti-map therapy, is knowledgeable about many of the practical questions regarding the anti-map therapy, and she is helpful.

Good luck, and let us know.


----------



## beyondSymptomManagement

Based on my personal experience, my risk/benefit made it very clear it was worth a try. Although it has not induced a permanent remission it has improved my symptoms greatly and kept me in a stable state.


----------



## Crohn2357

> David Graham, MD, a professor of medicine, molecular virology and microbiology at Baylor College of Medicine, in Houston, and his colleagues at 92 sites around the world conducted the MAP U.S. study, in which they randomly assigned 331 patients with moderately to severely active Crohn’s disease to receive either 95 mg of clarithromycin, 45 mg of rifabutin and 10 mg of clofazimine (RHB-104, RedHill Biopharma Ltd.) administered as five capsules twice daily for up to 52 weeks, or the same regimen of placebo pills.
> 
> “MAP U.S. is the first global, randomized trial to assess the efficacy of anti-MAP therapy in active [Crohn’s],” the team stated in an abstract they presented at the 2018 United European Gastroenterology Week (abstract LB06).
> 
> After 16, 26 and 52 weeks of treatment, Dr. Graham and his colleagues evaluated patients for clinical remission, which they defined as a Crohn’s Disease Activity Index (CDAI) score lower than 150. They also assessed clinical response, which was defined as a decrease of at least 100 points from baseline on the CDAI. Study participants continued any existing treatments throughout the trial.
> 
> According to the researchers, 42% of participants who received anti-MAP therapy along with their existing treatment achieved clinical remission at week 16, compared with 29% of placebo recipients (P=0.015). After 26 weeks, 37% and 23% of the two groups, respectively, were in clinical remission (P=0.007), whereas 44% of patients who received anti-MAP therapy achieved clinical response at 26 weeks, compared with 31% of placebo recipients (P=0.017).
> 
> Dr. Graham’s team found that 25% and 12% of anti-MAP and placebo recipients, respectively, were in clinical remission at the one-year mark of the study (P=0.003).
> 
> “RHB-104 was safe and well tolerated and could provide a new oral antibiotic therapy for use across a broad spectrum of Crohn’s disease patients,” Dr. Graham’s team concluded.
> 
> Although he welcomed the results, Dr. Shafran said he believed the study could have demonstrated a larger treatment effect if it had been designed differently.
> 
> “This trial included all-comers, not necessarily only those with MAP detected in their serum,” he said, adding that selecting only patients with confirmed MAP infection could have led to better outcomes.
> 
> Ira Kalfus, MD, a medical director at RedHill, said the study did not look at MAP status because no validated diagnostic tests are capable of accurately and reproducibly diagnosing the infection in humans.
> 
> “Detection of MAP via serological assays is challenging due to the low sensitivity of commercially available” tests, Dr. Kalfus said. “In humans, MAP is thought to reside intracellularly within macrophages, and serological antibody tests have limited utility in this situation.”
> 
> He said RedHill is researching whether polymerase chain reaction can be used to detect MAP in tissue samples.
> 
> Dr. Shafran also said that treating MAP early in the disease course could dramatically improve results. Many treatments for Crohn’s have relatively low rates of success, and patients who achieve initial response or remission often relapse within one year of treatment initiation.
> 
> “Antibiotics with a similar level of efficacy may be a good option to have for these patients,” Dr. Shafran said.
> 
> RedHill is completing a final analysis of the study data and meeting with FDA officials to discuss the results and determine how to move forward toward a New Drug Application.
> 
> “As soon as these discussions have been finalized, we will make them public,” Dr. Kalfus said.


https://www.gastroendonews.com/In-t...ent-Tops-Placebo-in-Large-Crohn-s-Trial/53847


----------



## Crohn2357

The Crohn's MAP vaccine is being tested on healthy people now, and the trial on Crohn's patients will begin soon.



			
				Article said:
			
		

> Volunteers, mainly made up of Crohn’s patients and their families also raised £700,000 for a diagnostic blood test to run in conjunction with the vaccine trials. Fundraising is still taking place to take the trials to completion.
> 
> The website says: “Historically, MAP in humans has been difficult to study as it cannot be seen under an ordinary microscope and is very difficult to grow.
> 
> “Testing for MAP by the presence of its DNA (using PCR) has found MAP in up to 92% of Crohn’s patients but until now no-one has developed a test to show MAP in-situ in the tissues of people with Crohn’s disease.
> 
> “With the new MAP test developed by Professor Hermon-Taylor, we are seeing it in intricate detail for the very first time.
> 
> “The test is an essential ‘companion diagnostic’ for the Vaccine trial; a simple blood test allowing doctors to confirm MAP infection prior to vaccination and monitor patients’ responses to the vaccine. Validation of the new test is almost complete”.
> 
> *Phase one trial of the second component of the vaccine is now underway on healthy volunteers and it is hoped phase two on Crohn’s patients will run in tandem, beginning at the end of April this year.
> 
> If all goes according to plan, trials should be completed by the middle of 2020. *
> 
> The vaccine has garnered huge support on social media sites including Facebook, Twitter and Instagram.
> 
> To find out more, visit www.crohnsmapvaccine.com


https://www.edinburghnews.scotsman....-crohn-s-disease-is-one-step-closer-1-4890394


Info on entry criteria:



			
				CMV Website said:
			
		

> *Can I be involved in the Vaccine trial? And when is the Vaccine likely to be available?*
> 
> A phase I safety trial in healthy human volunteers began in March 2017. This will be followed by a Phase IIa trial, anticipated to begin in the first half of 2019. The Phase IIa trial will be a single-centre trial based at St. Thomas’s Hospital, London, UK in 20 adults with Crohn’s Disease and will last 1 year. The estimated timeline of the Vaccine manufacture and trials is shown in the Gantt Chart below. The patients recruited to this trial will need to meet strict entry criteria; there are stringent regulations which we have to obey and the trial will be governed by the close scrutiny of the regulators. Regrettably we cannot invite people to take part in the trial at this time. However, the results of the trial will be analysed in real time as it proceeds. As soon as there is evidence of safety and efficacy, we can apply for use of the vaccine on compassionate grounds; this will enable people who wish to have the vaccine but are unable to be part of the trial to access it on a named-patient basis outside of the trial. Indeed, under the newly proposed ‘Early Access to Medicines’ scheme in the UK, severely ill patients who have failed existing treatments may be granted access to new medicines that are proven to be safe, even before efficacy has been fully established.  In addition, following the demonstration of safety and efficacy, it is anticipated that the Vaccine technology would be licenced to a pharmaceutical company to make it available to all who need it through health services worldwide -as part of this, larger Phase 3 trials inviting wider participation would be expected. The manufacture and trial of the Vaccine is being funded through investment in the company HAV Vaccines Ltd (HVL) -completion of the trial according to this timescale is dependent on HVL to secure the remainder of the funding required.
> 
> 
> 
> 
> 
> 
> 
> Timelines are current best estimates and are not set in stone. Delays are commonplace in research due to the unpredictable nature of organising and running trials (last updated 03.01.2019)


From: http://www.crohnsmapvaccine.com/faq/


----------



## Crohn2357

More info on the phase I trial (on healthy volunteers):
https://www.jenner.ac.uk/hav001-vaccine-trial
https://www.jenner.ac.uk/_asset/file/hav001-vis-3-0.pdf


 Crohn's MAP Vaccine March 2019 newsletter:  https://mailchi.mp/crohnsmapvaccine...e-cured-not-managed-shop-1740145?e=2f7cd0cabe


----------



## levi

Just curious if anyone could help me interpret my Otakaro Pathways (prelim) results. There are just too many specific and technical terms for me to nail down with proper certitude what the report is telling me. Thanks


----------



## Scipio

levi said:


> Just curious if anyone could help me interpret my Otakaro Pathways (prelim) results. There are just too many specific and technical terms for me to nail down with proper certitude what the report is telling me. Thanks


I can try.  Do you have a link to the results?


----------



## levi

Scipio said:


> I can try.  Do you have a link to the results?


I just have the PDF John emailed me. I'll add the info to this post. Not sure I should try posting the chart as I have a feeling the formatting will go haywire. If you think that will be helpful let me know and I'll see what I can do. Thanks!


Comments
No persister forms were seen, but several single large forms were noticed. This sometimes suggests latency of the
organism as a result of prior exposure to anti-TNFs (remicade, humira etc)
Persister forms
One possible grouping of a single mother -daughter cell was seen on extended screening
Daughter cells
There is a slight increase in ruptured forms when the 8 day reading is compared with the 30 day reading
Ruptured forms
Only one group of large forms was seen.
Large forms
The appearances are similar to those seen in Crohn's disease where the patient is not experiencing a flareup, but is on
sub-optimal therapy. The 7DN medium, which we are evaluating as a biomarker, was positive, and variant forms we
associate with Crohn's disease were seen.These variant forms were not robust in morphology and few in number. I have
seen similar appearances in treatment-resistant Crohn's disease -This can occur when most available therapies have
been exhausted. In that scenario, the patient may be experiencing a flareup, but the CWDM are difficult to culture.
Further culture work is planned.
Conclusions
INTERPRETATION

This was from the email:
This is a difficult sample to interpret, as there is little growth unless I look closely. (which I did). I am going to get some more cultures going, using novel growth promotants, to try and grow more DNA. Please contact me if you have any quesitons at this stage

It does seem odd that he mentions there is such little growth but also it appears similar to Crohn's and sub-optimal therapy. Seems like at least some tension between those two statements if not some contradiction. Also, this does seem like he found evidence of mycobacteria in general, not necessarily MAP specifically, is that correct? 

I haven't ever been on any anti-TNF drugs but did mention to him I consume DMSO which I've read at least one paper showing evidence it acts as a potent anti-TNF agent.


----------



## Scipio

levi said:


> It does seem odd that he mentions there is such little growth but also it appears similar to Crohn's and sub-optimal therapy. Seems like at least some tension between those two statements if not some contradiction. Also, this does seem like he found evidence of mycobacteria in general, not necessarily MAP specifically, is that correct?


I don't see those two statements as necessarily contradictory,  He appears to be saying that the specimen does not show signs of frank disease but does not look entirely normal either - perhaps some residual or latent disease can be seen.

He doesn't say anything one way or the other about whether it is specifically MAP.


----------



## levi

Scipio said:


> I don't see those two statements as necessarily contradictory,  He appears to be saying that the specimen does not show signs of frank disease but does not look entirely normal either - perhaps some residual or latent disease can be seen.
> 
> He doesn't say anything one way or the other about whether it is specifically MAP.



Thanks Scipio, that’s what I was afraid of on the second part. I was hoping it would be a definitive finding of MAP.


----------



## Crohn2357

Levi, I think John Aitken's results show MAP specifically, not mycobacteria in general.


----------



## Crohn2357

Anti-MAP therapies for Crohn's are getting more recognition in the mainstream media.

https://www.healthline.com/health/crohns-disease/cure

https://www.medicalnewstoday.com/articles/323072.php


----------



## Crohn2357

*A Cure for Crohn’s Disease — How Hopeful Should We Be?*

_A trial is under way for a vaccine to cure this chronic inflammatory condition._

https://www.everydayhealth.com/crohns-disease/treatment/cure-crohns-disease-how-hopeful-should-we/


----------



## Crohn2357

Jenner Institute published safety data for the Crohn's Map Vaccine.

http://www.crohnsmapvaccine.com/saf...t-simian-adenovirus-chadox2-vectored-vaccine/

https://twitter.com/ProfKatieEwer/status/1129010584979214336


----------



## Crohn2357

Anti-MAP therapy for Crohn's disease - Guy's and St Thomas' NHS ...

https://www.guysandstthomas.nhs.uk/resources/patient-information/gi/anti-MAP-therapy-for-Crohns.pdf


----------



## Crohn2357

*P550 Anti-mycobacterium paratuberculous therapy in Crohn’s disease: outcomes from tertiary IBD referral centres*
E Johnston S Honap B Al-Hakim J Sanderson

_Journal of Crohn's and Colitis_, Volume 13, Issue Supplement_1, March 2019, Page S389, https://doi.org/10.1093/ecco-jcc/jjy222.674
*Published: 25 January 2019*

Abstract

*Background*
Mycobacterium avium paratuberculosis (MAP), an obligate intracellular pathogen, has long been proposed as an aetiological factor in Crohn’s disease. Prolonged, combination antibiotic therapy has shown beneficial effect in the induction and maintenance of remission in a small number of studies but was not replicated in an RCT.1 However, the evidence remains conflicting, particularly with criticisms on experimental design and subtherapeutic antibiotic dosing in the latter. We report the outcomes of this therapeutic option in a selected cohort of patients at our institutions.

*Methods*
A retrospective study was conducted by examining the records of adult patients commenced on anti-MAP therapy (AMT) at both Guy’s and St. Thomas’ Hospitals and London Bridge Hospital, between February 2011 to December 2017. Treatment regimens were slightly varied but standard therapy was clarithromycin 750 mg OD, rifabutin 450 mg OD and clofazimine 100 mg OD. Hospital notes were used to capture demographic data, disease characteristics and therapy details including indications and duration of therapy. Objective measures of response included at least one of; reduction in CRP or faecal calprotectin, improvement in endoscopic or radiological appearances. Statistical analysis was performed using GraphPad Prism.
Results

In total, 62 patients were prescribed AMT over the study period, 21 were excluded due to insufficient outcome data. 21/41 (51%) were male and median age was 28 (range 18–63) at the time of commencing therapy. The cohort had moderate to severe Crohn’s disease with 26 (63%) having stricturing or penetrating disease and 18 (44%) with previous surgery. Thirty-one (76%) had previously received biologic therapy. AMT was commenced in 26 (63%) patients due to failure of conventional therapy, 3 (7%) in patients where conventional therapy was not appropriate and the remaining due to patient preference. AMT was well tolerated with only 5 (12%) patients stopping therapy due to adverse effects. Nineteen patients (46%) demonstrated at least partial benefit, corroborated by objective evidence in 13/19 (68%). Response was not associated with disease phenotype and duration, previous therapy or use of clofazimine. Those patients who responded had a longer duration of therapy (median 24 months compared with 14 months; p = 0.04) than patients who did not respond.

*Conclusions*
Our study demonstrates that in a cohort of patients in which the majority failed conventional treatment, AMT was well tolerated and a response was seen in 46%. Patients who responded were on AMT a median 24 months which supports the current recommendation of a 24-month duration of treatment. Limitations include a small, heterogenous cohort of patients.

Reference

1. Selby WS, Pavli P, Crotty B, et al. Two-year combination antibiotic therapy with clarithromycin, rifabutin, and clofazimine for Crohn’s disease. Gastroenterology 2007;132:2313–9.


----------



## Crohn2357

South East London Area Prescribing Committee - NHS Lambeth CCG

www.lambethccg.nhs.uk/news-and-publ...ion 066 anti MAP therapy for IBD May 2017.pdf


----------



## Crohn2357

Crohn2357 said:


> Jenner Institute published safety data for the Crohn's Map Vaccine.
> 
> http://www.crohnsmapvaccine.com/saf...t-simian-adenovirus-chadox2-vectored-vaccine/
> 
> https://twitter.com/ProfKatieEwer/status/1129010584979214336


A review of the results of this study by Dr. Tim Bull: 
https://humanpara.org/expert-review-crohns-map-vaccine-may-2019-research-paper/


----------



## Crohn2357

MAP: Just a Suspect or Proven Perp in Crohn’s?
Debate over mycobacterium paratuberculosis as major CD cause mirrors Helicobacter pylori saga 

https://www.medpagetoday.com/readin...9or6hhvzwntzbyf0r0gvlrdgklijmrmzehvoxayj5fic4


----------



## Crohn2357

*



			British Society of Gastroenterology updates guidance on Crohn’s
		
Click to expand...

*


> We are pleased to share the recently published updated guidance on Crohn’s and Ulcerative Colitis for adults over sixteen from the British Society of Gastroenterology. It includes the first ever mention of RHB-104, the  combined antibiotic pill which has been successfully trialled by Redhill Biopharma; this large RCT addresses the mycobacteria which we believe is at the root of the Crohn’s disease and which the Crohn’s MAP Vaccine is also designed to target. We are delighted to see antibiotic treatment included in the new guidance and hope  that the BSG will be following the progress of the vaccine trials with interest!











						British Society of Gastroenterology updates guidance on Crohn's - Crohn's MAP Vaccine
					

We are pleased to share the recently published updated guidance on Crohn’s and Ulcerative Colitis for adults over sixteen from the British Society of Gastroenterology. It includes the first ever mention of RHB-104, the  combined antibiotic pill which has been successfully trialled by Redhill...




					www.crohnsmapvaccine.com


----------



## Crohn2357

Chrons Ma said:


> Son was tested by Otakaro Pathways, and subsequently became a patient of Prof. Tom Barody (CDD, Sydney), using anti-biotic anti-map therapy. Unfortunately,  our son is not one of the success stories, but there are many for whom this treatment does work. Research does back the theory, with the para-physiology of Johnnes in cattle identical to Crohns in humans. Toms "poster" patient is a woman now in her 30's, living a full life in complete remission for years. Kimberly was 17 when she became one of Tom's first patients, when anti-map was in its infancy. She had been told she needed a total colectomy as her lower GI was beyond repair, and she would never have children. A remarkable success story indeed.
> 
> I am pleased we partook in the treatment, for though it was unsuccessful for our son, if we had not tried, it would always have been a "what-if" for us. (And I do wonder whether there were other factors involved in his particular lack of success with the treatment, but this is another story all together)
> 
> The research into gut bacteria and the implications on our health is being more widely researched now, with strong links to other diseases, including the likes of Parkinsons, Alzheimers and even cardio-vascular implications


----------



## Crohn2357

Crohn's MAP Vaccine March 2019 newsletter said:
			
		

> *Phase 2 Clinical Trial in people with Crohn's disease*
> 
> The trial will be conducted at Guy’s and St Thomas’s Hospitals in patients with mild Crohn's Disease (with a positive test for MAP) aged between 18-50 years who are not taking any immunosuppressant medications or biologics and are resident in the UK. The trial design will be similar to the Phase 1 Clinical Trials in Oxford and will concentrate again, as required, on Safety and Immunogenicity. We will be using our new MAP test to assess MAP levels before and after vaccination. Further details of the eligibility criteria will be published online when the trial opens for recruitment. Please note that recruitment has not yet started, so we therefore ask our supporters not to contact us or St Thomas’ Hospital about this.





			World MAP Day special edition newsletter March 2019


----------



## Crohn2357

> *CLOFAZIMINE: PRACTICAL CONSIDERATIONS FOR PATIENTS*
> 
> _The information provided is not intended or implied to be a substitute for professional medical advice, diagnosis or treatment. You are encouraged to confirm any information obtained from or through this website with other sources, and review all information regarding any medical condition or treatment with your physician. Human Paratuberculosis Foundation does not recommend, endorse or make any representation about the efficacy, appropriateness or suitability of any specific tests, products, procedures, treatments, services, opinions, health care providers or other information that may be contained on or available through this website_.
> *Introduction*
> Due to the recent success of RedHill Biopharma’s Stage 3 trial of RHB-104, more patients and doctors have become interested in Atypical Mycobacterial Antibiotic Therapy  (AMAT) as a treatment option for chronic immune conditions, such as Crohn’s disease and multiple sclerosis. RHB-104 contains a triple combination of antibiotics that showed significant effectiveness in Crohn’s disease, and includes clarithromycin, Rifabutin and clofazimine. While clarithromycin and Rifabutin are easily available worldwide, clofazimine is not.
> *Limited Availability of Clofazimine*
> 
> 
> 
> 
> 
> Clofazimine was first developed by researchers at Trinity College in Dublin, Ireland. It’s primary use is for the treatment of leprosy. It is also used to treat nontuberculous mycobacterial infections. With its inclusion in RHB-104, there developed a growing niche for the drug in Crohn’s disease. But this medication is not readily available at pharmacies or chemists, because few cases of leprosy exist in the Western world.
> Clofazimine has been classified as an orphan drug, which means that few companies produce the medication due to limited potential for profitability. It does not mean that the drug is illegal, or has been banned. A community member has kindly provided Human Para with a variety of options he considered on his quest to legally obtain clofazimine.
> 
> *Option 1:  FDA SPIND (Single Patient Investigational New Drug) via Expanded Access*
> 
> 
> 
> 
> 
> In recent years, the United State Food & Drug Administration (FDA) has taken a more lenient approach in allowing doctors and their patients to make decisions about treatments that have not yet received full FDA approval for a specified condition. This practice is known as Expanded Access, or Compassionate Use. While clofazimine is FDA approved for leprosy, it is not yet approved for use in Crohn’s disease. Prescribing an FDA approved drug  for a secondary, unapproved condition is considered an “off label” use of that medication, and can be a legal gray area for doctors. If approval is granted, the FDA will issue a SPIND # to the investigating physician, for use with the patient named in the protocol.
> In parallel, Novartis, the Swiss pharmaceutical manufacturer of clofazimine, has developed its own Managed Access Program. Through Managed Access, Novartis is able to work directly with physicians (but not patients) to guide them thru the necessary regulatory steps. Once the SPIND # is assigned by the FDA, they arrange access for your clinic to clofazimine.
> In our case, our gastroenterologist developed her plan/protocol, based on the RedHill MAPUS Clinical Trial protocol and input provided by Prof. Borody. The University required signature approval of several of colleagues, which she received. The request was also approved by the Institutional Review Board (IRB).
> Following IRB approval, our doctor submitted the package, along with a few other completed forms, to the FDA for approval under Expanded Access. This was a relatively straightforward process. From the time the protocol was developed it took 4-6 weeks to get IRB signatures, and FDA approval.
> Novartis required hard copies (not email) of the various approvals, after which they arranged shipment of the clofazimine directly to the clinic. The approach is sometimes seen as a “trial of n=1.”
> *Option 2: Prof. Thomas Borody, Centre for Digestive Diseases in Sydney, Australia*
> Professor Borody’s clinic in Sydney has a relationship with a compounding pharmacy for providing clofazimine to Crohn’s disease patients worldwide. By contacting their office, your physician can work with the staff to complete case histories, prescriptions, and arrange 90-day shipments, at a fixed cost. NOTE: Your physician must contact the CDD directly via email, phone or fax. Due to the volume received, inquiries from patients cannot be answered.
> *Option 3:  Order Online from Canadian Pharmacies*
> A Google search for clofazimine will reveal dozens of offers from Canadian online pharmacies, promising to provide clofazimine to United States patients, worry free. While there are hundreds of such online pharmacies, the (supposedly) most reliable have certification or approval from two agencies: CIPA and Pharmacy Checker.
> CIPA, the Canadian International Pharmacy Association, has authorized 66 Canadian websites to display its seal, which sites are licensed and regulated by the government for safety.
> Pharmacy Checker has a verification program where they check the licensing and industry standards of applicants to assure they are in good standing in the countries in which they are located. Unlike CIPA, Pharmacy Checker is open to pharmacies around the world. Pharmacies in certain countries are subject to onsite inspection.
> We looked at every online pharmacy that had either CIPA approval, Pharmacy Checker approval, or both. Of more than 80 sites checked, only 8 offered clofazimine. Some of these sites appeared to be owned by the same person. A few of those that offered clofazimine accepted credit card payments, but some only accepted a check or payment via Paypal. This could be a consideration, and a possible red flag. The pharmacies we checked stated they received their supply from India. China is also another possible supplier.
> While the easiest of the three options above, supply chain and verification methods may be an issue for some patients. Additionally, for Canadian patients, these online pharmacies are not available since they are (ironically) prohibited from shipping to Canadian residents. Lastly, any international mail order medication is subject to customs inspection, which may delay delivery.
> _Thank you to Kerry Schuster for sharing his journey and providing our community with this resource._











						Clofazimine: Practical Considerations for Patients
					

One man's journey to legally obtain clofazimine for the treatment of Crohn's disease using Atypical Mycobacterial Antibiotic Therapy (AMAT).




					humanpara.org


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## Crohn2357

The MAP Gap Newsletter | July 2019 | Human Paratuberculosis Foundation
					

All the latest news and research about Mycobacterium avium subsp. paratuberculosis (MAP) and the treatment of Crohn's and other diseases using AMAT therapy.




					humanpara.org


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## Crohn2357

> RedHill plans to meet with the FDA in the second half of 2019 to discuss the development path toward potential approval of RHB-104, including the design of a confirmatory Phase 3 study. The MAP US randomized, double-blind, placebo-controlled first Phase 3 study with RHB-104 for Crohn’s disease successfully met both its primary endpoint and its key secondary endpoints and presented the broad benefit of RHB-104 as an add-on therapy to standard-of-care treatments for Crohn’s disease, including anti-TNFs.








						RedHill Biopharma Receives Allowance for New U.S. Patent Covering RHB-104 for Crohn’s Disease and RHB-204 for NTM Infections | 2019 | News | RedHill
					






					www.redhillbio.com


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## Crohn2357

Expert Rev Clin Immunol. 2011 Nov;7(6):751-60. doi: 10.1586/eci.11.43.
*Primary treatment of Crohn's disease: combined antibiotics taking center stage.*
Chamberlin W1, Borody TJ, Campbell J.
*Author information

Abstract*
Although controversial, the use of properly chosen antibiotics in Crohn's disease appears beneficial. Evidence supporting the use of targeted antibiotic therapy comes in two forms: statistical evidence derived from meta-analyses of multiple formal studies and the documented clinical and endoscopic responses in patients treated with antibiotic combinations outside of formal clinical studies. This article reviews evidence from both categories that support the use of properly chosen antibiotic regimens in treating Crohn's disease, comments on the advantages and disadvantages of antibiotic therapy, and attempts to present a unifying hypothesis related to the role of enteric bacteria, mucosal immunity and antibiotic therapy. Relevant studies identified through a Medline search from 1976 to 2011 were assessed for inclusion by two independent observers who resolved any disagreements by consensus. References from all identified articles and recent review articles were cross-checked to ensure a thorough search. Papers were selected based on scientific merit as to which presented original contributions to the results.








						Primary treatment of Crohn's disease: combined antibiotics taking center stage - PubMed
					

Although controversial, the use of properly chosen antibiotics in Crohn's disease appears beneficial. Evidence supporting the use of targeted antibiotic therapy comes in two forms: statistical evidence derived from meta-analyses of multiple formal studies and the documented clinical and...




					www.ncbi.nlm.nih.gov
				






> In 2011, Dr. William Chamberlin, Prof. Thomas Borody and Dr. Jordana Campbell collaborated on a meta-analysis of the published Medline studies from 1976 to 2011 which discussed Crohn’s disease patients treated with antibiotic combination therapy. The article, Primary Treatment of Crohn’s Disease: Combined Antibiotics Taking Center Stage, gives unbiased data on the effectiveness of antibiotic use in Crohn’s disease. For those of you who are short on time or find this type of technical reading difficult, we have attempted to summarize the key points.











						Primary Treatment of Crohn's | Human Paratuberculosis Foundation
					

Dr. Chamberlin, Prof. Borody and Dr. Campbell collaborate on a meta-analysis of the published studies on Crohn's disease patients treated by antibiotic therapy.




					humanpara.org
				




View Full Text:








						Primary Treatment of  Crohn's Disease
					

The rationale for using antibiotics as primary treatment of Crohn's disease is based on increasing evidence that gut bacteria are the root of the problem, but will they help or hinder -- in the long run?



					www.medscape.com
				




Download Full Text:








						(PDF) Primary treatment of Crohn’s Disease--Combined antibiotics taking center stage
					

PDF | Although controversial, the use of properly chosen antibiotics in Crohn's disease appears beneficial. Evidence supporting the use of targeted... | Find, read and cite all the research you need on ResearchGate




					www.researchgate.net


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## Crohn2357

Human Paratuberculosis Foundation's twitter page:



			https://twitter.com/HumanPara


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## Crohn2357

_



			I was diagnosed with Crohn’s Disease in 2004. After the ‘shock’ wore off, I began researching the disease and came across Borody’s and Hermon-Taylor’s research. This prompted me to ask my GI specialist for a blood test to check for MAP. He ignored my requests, dismissed the compelling evidence and continued treating me with steroids and 5-ASA’s. It wasn’t long before these treatments were no longer effective… not to mention the side effects. I took matters into my own hands and sought out Dr. Saleh Naser at UCF. After several months of communication, he finally agreed to test me for MAP (I can’t thank him enough!). Needless to say, I tested positive and finally had the proof. I took the results of the MAP positive test to an Infectious Disease specialist and he began treating me with anti-MAP antibiotics under the premise that I have an ‘atypical mycobacterium infection’. The logic being the MAC (Mycobacterium Avium Complex) is recognized as disease-causing in humans, thereby bypassing the Crohn’s/MAP argument. The protocol includes clarithromycin, rifabutin and clofazimine (the same combo found in RHB-104). Since beginning this treatment, I have been in remission. In short, I had to do an ‘end around’ on traditional thinking to get the correct treatment. While it has saved me from adalimumab and surgery, it has not been able to eradicate the infection. My hope is that it will sustain me until the vaccine is available. Thanks again to Amy and her father for their tireless efforts!!!
		
Click to expand...

_








						Testimonials - Treatment for Crohn's and MAP - Crohn's MAP Vaccine
					

Testimonials in support of MAP and its association with Crohn’s Disease; anti-MAP therapy as a treatment for Crohn’s and support for the Crohn’s MAP Vaccine as a potential cure. I was diagnosed with Ulcerative Colitis as a freshman in college. Within 5 years the illness progressed to Crohn’s...




					www.crohnsmapvaccine.com


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## Crohn2357

> _The recently published article describing the discovery of a MAP mutation that may lead to the development of a MAP vaccine for both animals and humans was received by our community with great interest. One of the researchers, Dr. William C. Davis, has provided Human Para with a summary of this highly technical article. A huge thanks to Dr. Davis and his colleagues for this piece, and for their contribution to MAP science._
> 
> ...
> 
> "The results at this stage of our studies are very promising. *The finding that deletion of a single gene cripples Map’s ability to establish a persistent infection led to the discovery of a peptide with potential for development of a peptide-based vaccine. Studies with the peptide in tissue culture show vaccination leads to development of immune cells that can kill Map inside macrophages, an essential requirement for a vaccine against intracellular pathogens. *While this is being investigated in cattle, it could have implications for human health as well."











						A possible peptide-based vaccine for MAP | Human Para Foundation
					

Dr. William C. Davis summarizes the discovery of a MAP mutation that may lead to the development of a MAP vaccine for both animals and humans




					humanpara.org
				






> *Research Summary*
> 
> The long term objectives of our research program are to elucidate the mechanisms regulating the immune response to infectious agents and develop protective vaccines. To achieve these objectives, we continue to develop and use monoclonal antibodies and assays to study the immune response in domestic animals with a primary focus on ruminants. M. avium subsp. Paratuberculosis (Map) has been selected as the model pathogen for our investigations because of its economic importance and its potential for providing insight into the mechanisms regulating the immune response to Map and other intracellular pathogens. Map is the causative agent of Johne’s disease (JD) in cattle, a chronic wasting disease of the intestine. It causes significant economic loss to producers, especially the dairy industry, due to increase in forage consumption, decreased milk production and early culling due to poor health of affected animals. There is also a concern that Map is a zoonotic pathogen. Map has been isolated from human patients with Crohn’s disease (CD), a chronic inflammatory disease of the intestine. It is not clear whether Map is the etiologic agent causing Crohn’s disease. However, recent studies on CD and mycobacterial pathogens M. tuberculosis (Mtb) and Map have shown a similarity in the mechanisms of pathogenesis at the cellular and molecular level. The studies have revealed the cross regulation of the immune system by regulatory T cells and effector T cells mediating protective immune responses is dysregulated, giving rise to an imbalance that results in chronic inflammation of target tissues, and in the case of Mtb and Map dysregulation of protective immunity. To extend these observation we developed a bovine cannulated ileum model to conduct studies on the mechanisms of pathogenesis mediated by Map in the natural host, studies that cannot be conducted in humans. The model has offered an opportunity to study the interaction of Map during the early and late stages of infection. We have also developed and used a flow cytometric assay to analyze the immune response to Map and methods to elucidate the functional changes associated with dysregulation of the immune system. Use of these methods in conjunction with development of methods to monitor the intracellular killing of bacteria by cytotoxic T cells have facilitated analysis of the functional activity of cytotoxic T cells responding to Map and derived candidate antigens. Ongoing studies with a mutant of Map, with a deletion in relA, has shown deletion abrogates the capacity of the mutant to establish a persistent infection. Further studies have shown the target of the immune response is directed towards a membrane protein (MMP). Ex vivo studies have shown stimulation with the MMP leads to the development of cytotoxic T cells with the capacity to kill intracellular bacteria. This major finding indicates a peptide based vaccine is possible against a major pathogen. These findings will now be used to advance our studies to the next phase, development and validation of a virus vector containing the gene encoding the MMP as a vaccine for JD.





			https://vmp.vetmed.wsu.edu/people/faculty/profile/william-c-davis
		











						MAP protein may aid battle against Johne's disease
					

Vaccine investigators use Johne's disease-causing bacterium's own protein against it.




					www.feedstuffs.com


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## Crohn2357

William C. Davis, J. Todd Kuenstner & Shoor Vir Singh                                    (2017)                                    *Resolution of Crohn’s (Johne’s) disease with antibiotics: what are the next steps?*,                                    Expert Review of Gastroenterology & Hepatology,                                                                                                                                                                                                    11:5,                                        393-396,                                                                        DOI: 10.1080/17474124.2017.1300529
(Free access to full text)


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## Crohn2357

Redhill's latest press release clearly shows their RHB104 phase 3 results.
					

Hard to understand people's reluctance to consider this treatment. Please see page 22-34 for relevant info: https://ir.redhillbio.com/static-files/f465e5e9-5f4d-4f71-9584-b7958715e8d5?fbclid=IwAR2upo2HGLH-hrwNJBgJEKmpBvOShD7sppnGWgOHN9tKLQ0kMJVApcwzO0A



					www.crohnsforum.com


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## Crohn2357

kiny said:


> https://academic.oup.com/ibdjournal/article-abstract/25/4/711/5218864?redirectedFrom=fulltext
> 
> _Inflammatory Bowel Diseases_, Volume 25, Issue 4, April 2019
> 
> Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.
> 
> Oberc, Fiebig-Comyn, Tsai CN, Ethenawy W, Coombed BK
> 
> *Antibiotics Potentiate Adherent-Invasive E. coli Infection and Expansion
> 
> ''BACKGROUND:*
> _Crohn's disease (CD) is an inflammatory bowel disease with a complex etiology. Paradoxically, CD is associated with the use of antibiotics and with an increased abundance of an unusual phenotypic group of Escherichia coli known as adherent-invasive E. coli (AIEC). However, the impact of antibiotics on AIEC infection has not been well studied in controlled models of infection.
> 
> *METHODS: *
> We infected mice with AIEC before or after treatment with a variety of different classes of antibiotics. We assessed levels of AIEC in the feces and tissues, AIEC localization by immunofluorescence microscopy, and tissue pathology.
> 
> *RESULTS: *
> We found that a wide range of antibiotic classes strongly potentiated initial AIEC infection and expanded AIEC in chronically infected mice. We found that the ability of antibiotics to potentiate AIEC infection did not correlate with a stereotyped shift in the gut bacterial community but was correlated with a decrease in overall diversity and a divergence from the pre-antibiotic state. We found that antibiotic-induced inflammation provided a fitness advantage for AIEC expansion through their use of oxidized metabolites in the postantibiotic period.
> 
> *CONCLUSIONS: *
> Our results show that antibiotics can render hosts more susceptible to initial AIEC infection and can worsen infection in previously colonized hosts. AIEC appears to exploit host inflammatory responses that arise in the postantibiotic period, highlighting a previously unknown interaction between CD risk factors.''_








						The dangers using the wrong antibiotics that are ineffective against AIEC.
					

https://academic.oup.com/ibdjournal/article-abstract/25/4/711/5218864?redirectedFrom=fulltext  Inflammatory Bowel Diseases, Volume 25, Issue 4, April 2019  Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada.  Oberc, Fiebig-Comyn, Tsai CN, Ethenawy W...



					www.crohnsforum.com


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## Crohn2357

Crohn's MAP Vaccine September 2019 newsletter

View this email in your browser














*Research update*
*Vaccine Trials Progress:*
*Phase II Clinical Trial in people with Crohn's disease:

Drumroll… We are excited to report that the Phase II trial in Crohn’s disease has received MHRA approval to proceed!! *

We are still awaiting a decision from the Research Ethics Committee (REC) which is the other major mandatory approval required for any trial to begin. We hope that the trial will be able to start around end October/early November 2019.

The trial will be conducted at Guy’s and St Thomas’s Hospitals in 28 patients with:

mild Crohn's Disease (with a positive test for MAP) 
aged between 18-50 years 
not taking any immunosuppressant medications or biologics
resident in the UK and receiving their usual Crohn’s disease care at Guy’s and St Thomas’s trust 
Please note that these are not the full eligibility criteria; these will be published online when the trial opens for recruitment. Recruitment has not yet started, so we therefore ask our supporters not to contact us or St Thomas’ Hospital about this.

The trial design will be similar to the Phase 1 Clinical Trials in Oxford and will concentrate again, as required, on Safety and Immunogenicity. We will be using our new MAP test to assess MAP levels before and after vaccination. Further updates will be posted online, so please check the website regularly as there won't be another newsletter before Christmas.

Dr Gaurav Agrawal is a consultant gastroenterologist working with the team at St Thomas’s. Like us, he is feeling very positive about the trial:





"I have been collaborating with Professor Hermon-Taylor for a number of years now and have always believed the science behind the MAP diagnostic test and the vaccine. I am helping to organise the trial to be run at Guy’s Hospital and to assess the impact and safety of the vaccine in Crohn’s sufferers. I have a fantastic team to work with. For me there are two tragedies surrounding Crohn’s disease. First is the impact on sufferers and that people are severely debilitated by this disease. Secondly, that the science behind it is misunderstood, which means that an effective therapy is being ignored. This project will create a paradigm shift in our understanding of Crohn’s. Not only will we provide evidence of MAP causality, but also the creation of a novel therapy to alleviate this condition and many others. It is so important to me that people all over the world support this project, it couldn’t have been done without you. Your support is not only physical and monetary but more importantly emotional. It gives us independence and persistence to overcome obstacles in order to give a better life for so many people."

*Phase 1 Safety Trials in healthy volunteers (people who do not have Crohn's disease):*

The Jenner Institute, Oxford have recently reported the preliminary data from the prime/boost element of the Phase 1 trial. We are pleased to report that, in those volunteers who have received both vaccines, the MVA HAV vaccine significantly boosted the T cell immune response to prime vaccination. This is the first time that the effect of the full treatment (ie. both vaccine shots given 8 weeks apart) has been seen in humans. This study has yet to be completed and the data will need to be thoroughly analysed at completion. However, we are very encouraged by the results so far!

Full details of this trial.
*MAP test update*
The validation work on the MAP test is being prepared for publication and the team will be in a position to submit the paper to an appropriate journal the before the end of 2019.

This is what Neil, our senior research scientist, has to say about our recent progress:
"This year has been a busy one in the lab. We recently submitted a grant to the prestigious Rutherford Appleton Laboratory (RAL) in Harwell, Oxfordshire. The aim of this application was to enable us to make use of the super resolution microscopy facilities at the institute, and by doing so increase our understanding of MAP at a cellular level… and get better pictures of MAP under the microscope for our upcoming paper. I’m very pleased to say that we were successful in our application and I’m looking forward to generating some more important data to support our current research. We have also been working towards perfecting techniques that will enable us to generate further data for our antibody validation. Although a lengthy process, such stringent techniques are essential for these reagents to be accepted in future publications on the MAP Vaccine. With the lab work progressing at a fast pace and with the successful application to undertake some ‘state of the art’ microscopy studies at the RAL, spirits are high! It means a lot to us that there are people out there donating hard earned cash to fund this research, as without your support none of this valuable work would have been possible."

Sadly, the institution-wide grant application (led by our team) to the Wellcome Trust for funding to purchase a super-resolution confocal microscope (like the one we will be using at RAL) for King’s College London was unsuccessful. However, we will be resubmitting the proposal to another major funder… so fingers crossed for second time lucky!

We are also currently running a study comparing MAP test results in 30 patients with Crohn’s disease versus 30 healthy controls. This is important as there are very few studies looking at the proportion of healthy people who carry MAP asymptomatically (in other words as a ‘latent’ infection in the same way that may people worldwide have ‘latent TB).  As with the vaccine trial, these volunteers will be chosen from St Thomas's existing patient lists.



*Fundraising*
Fundraising continues as we head into the phase 2 trial. This funding is needed to keep the lab going so that MAP levels can be tracked during the trial period and so that validation of the long awaited MAP blood test can be completed. There are too many fundraisers to mention here but we are so grateful to each and every one of you who has supported the research. Here are two recent examples of your fundraising events:-






In May, Anna Sykes posted: “My husband's grandad, who is 100 in November, has been having a clear out at home. He's got 2 great grandsons with Crohn's so has donated some items to be sold to raise money for the vaccine. We will let you know how much we raise but the Lladro figurines that were kindly donated by Great-Grandad Sykes have been sold on ebay and have raised an amazing £187 so far. We also received an extra donation from a supporter in Austria whilst raising this money so a huge thank you to her.”






In April, Christine Clifford held a raffle to win a beautiful keepsake Fimo picture created by the talented Natalie Haddock of Handmade Fimo Cake Toppers and
Keepsake Gifts . Winner Alexia Emmerson and her daughters were delighted with their picture. A total of over £200 pounds was raised.






Inspired? If you’d like to start a fundraiser of your own, you can find the instructions here (Please note that the pdf needs updating). The suffix code for the vaccine is now TS11359. This is the tag required to ensure that funds go to the Crohn’s MAP Vaccine test research within King’s College London. Example:
https://www.justgiving.com/fundraising/appointments-ts11359 )

The TS11359 code should also be noted on the back of cheques sent to King’s College London (the old one, MEN 9150, is out of date). We have recently amended the Gift Aid form to include this number too.

It has been a very long journey but we are so close now. With your ongoing support, we WILL get this job done!

Our fundraising total as of 17 th September is £ £781,242. As you can see from Neil’s report, this is being put to very good use!







*Useful links*
If anyone would like more detail about the fundraising structure of this project, please click here.
For our scientific ‘Core Literature pack’ please click here.
To find out how to become a hero click here.









We know of no other charity like this. We are determined to bring an end to Crohn’s.

Please continue to help us.

Thank you
The Crohn’s MAP Vaccine team


----------



## Crohn2357

*RedHill Announces Full Results from MAP US Phase 3 Study and Supportive Top-Line Results from MAP US2 Study with RHB-104 in Crohn’s Disease*
11 October, 2019
*TEL-AVIV, Israel and RALEIGH, N.C., October 11, 2019* RedHill Biopharma Ltd. (Nasdaq: RDHL) (Tel-Aviv Stock Exchange: RDHL) (“RedHill” or the “Company”), a specialty biopharmaceutical company primarily focused on the development and commercialization of clinical late-stage, proprietary drugs for the treatment of gastrointestinal diseases, today announced  full Week 52 results for all subjects in the previously announced positive Phase 3 randomized, controlled study of RHB-104 in Crohn’s disease (the “MAP US study”) and supportive top-line results from the open-label extension Phase 3 study (the “MAP US2 study”).
The full Week 52 results of blinded treatment in the MAP US Phase 3 study with RHB-104 were consistent with the previously reported positive outcomes of the study. The study continued to meet its primary endpoint of clinical remission (CDAI < 150) at week 26 (36.7% vs. 22.4%, p=0.0048), key secondary endpoints of maintenance of remission at weeks 16 and 52 (25.9% vs. 12.1%, p=0.0016) and, notably, durable clinical remission on all visits, week 16 through 52 (18.7% vs. 8.5%, p=0.0077, RHB-104 vs. placebo, respectively).
In the analysis of the complete safety information for the study, a top-line electrocardiogram (ECG) monitoring report for the MAP US study recently received and shared with FDA, demonstrated evidence of progressive prolongation of the QTcF interval across visits, with the largest placebo-corrected ΔQTcF (∆∆QTcF) of 30.6 ms at Week 52 of treatment with RHB-104. None of these QT abnormalities resulted in adverse cardiac events. Clofazimine, as well as clarithromycin (another active component of RHB-104) are known to be associated with QT prolongation. RedHill continues to analyze the data from the RHB-104 studies, including QT prolongation findings and various pharmacokinetic and pharmacodynamic models and, as previously announced, intends to meet with the FDA again in the coming months to discuss the RHB-104 program, including these data. 
The MAP US2 open-label extension Phase 3 study evaluated the safety and efficacy of RHB*-*104 in subjects from the MAP US study with persistent active Crohn’s disease (Crohn’s Disease Active Index (CDAI) ≥ 150) after 26 weeks of blinded study therapy. A total of 54 subjects entered the open-label extension study and 30 subjects completed 52 weeks of treatment.
Interim top-line results from the MAP US2 study demonstrated 27.8% clinical remission with RHB-104 at week 16 and 22.2% remission at week 521. Of the MAP US2 subjects who were previously randomized to the placebo arm (as an add-on to standard-of-care therapies) in the MAP US study and treated with RHB-104 for the first time in the MAP US2 study, 31.6% achieved remission at week 16 and 26.3% achieved remission at week 52. These results further support the potential clinical benefit of treatment with RHB-104 in Crohn’s disease patients.
RHB-104 was found to be generally safe and well tolerated. The incidence of treatment emergent adverse events, serious adverse events and reported adverse events leading to discontinuation in the MAP US2 study were lower than in the active arm of the MAP US study (77.8% vs. 87.3%, 7.4% vs. 18.7% and 9.3% vs. 21.1%, respectively). Similar trends were observed in MAP US2 subjects who received concomitant anti-TNFs, consistent with the safety of treatment with RHB-104 in combination with anti-TNF agents.
The top-line results and subsequent analyses were provided to RedHill by an independent third party following an independent analysis and remain subject to completion of the independent review and analysis of the underlying data, including all safety, secondary and other outcome measures, and completion of the Clinical Study Report (CSR).
The clinical studies with RHB-104 are registered on www.clincaltrials.gov, a web-based service of the U.S. National Institute of Health, that provides access to information on publicly and privately-supported clinical studies.
*
About RHB-104:*
RHB-104 is a proprietary, orally administered antibiotic combination therapy, with intracellular, antimycobacterial and anti-inflammatory properties. The randomized, double-blind, placebo-controlled, first Phase 3 study with RHB-104 in Crohn’s disease (the MAP US study) successfully met both its primary endpoint and key secondary endpoints and presented the benefit of RHB-104 as an add-on therapy to standard-of-care treatments for Crohn’s disease, including anti-TNF agents. The company also reported supportive top-line results from an open-label extension Phase 3 study (MAP US2) evaluating the safety and efficacy of RHB*-*104 in subjects with persistent active Crohn’s disease after 26 weeks of blinded study therapy in MAP US. RHB-104 was developed based on the hypothesis that Crohn’s disease is caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection in susceptible patients. The development of RHB-104 is consistent with the growing awareness of the possibility that a bacterially-induced dysregulated immune system may contribute to the pathogenesis of various autoimmune diseases of unknown etiology.
*
About RedHill Biopharma Ltd. *
RedHill Biopharma Ltd. (Nasdaq: RDHL) (Tel-Aviv Stock Exchange: RDHL) is a specialty biopharmaceutical company, primarily focused on the development and commercialization of clinical late-stage, proprietary drugs for the treatment of gastrointestinal diseases. RedHill commercializes and promotes several gastrointestinal products in the U.S.: *Donnatal®* *- *a prescription oral adjunctive drug used in the treatment of IBS and acute enterocolitis; *EnteraGam®* *-* a medical food intended for the dietary management, under medical supervision, of chronic diarrhea and loose stools and *Mytesi®* *-* an anti-diarrheal drug indicated for the symptomatic relief of non-infectious diarrhea in adult patients with HIV/AIDS on antiretroviral therapy. RedHill’s key clinical late-stage development programs include: (i) *RHB-105 (Talicia®)* for the treatment and eradication of Helicobacter pylori infection with a U.S. NDA submitted and accepted for priority review with a target PDUFA action date of November 2, 2019; (ii) *RHB-104,* with positive top-line results from a first Phase 3 study for Crohn's disease; (iii) *RHB-204, *with a planned pivotal Phase 3 study for pulmonary nontuberculous mycobacteria (NTM) infections; (iv) *RHB-102* (*Bekinda®*)*,* with positive results from a Phase 3 study for acute gastroenteritis and gastritis and positive results from a Phase 2 study for IBS-D; (v) *Yeliva® (ABC294640),* a first*-*in*-*class SK2 selective inhibitor, targeting multiple oncology, inflammatory and gastrointestinal indications, with an ongoing Phase 2a study for cholangiocarcinoma; (vi) *RHB*-*106,* an encapsulated bowel preparation licensed to Salix Pharmaceuticals, Ltd. and (vii) *RHB-107, *a Phase 2-stage first-in-class, serine protease inhibitor, targeting cancer and inflammatory gastrointestinal diseases. More information about the Company is available at: www.redhillbio.com.

This press release contains “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements may be preceded by the words “intends,” “may,” “will,” “plans,” “expects,” “anticipates,” “projects,” “predicts,” “estimates,” “aims,” “believes,” “hopes,” “potential” or similar words. Forward-looking statements are based on certain assumptions and are subject to the Company’s continuing review and quality control analysis of clinical data  various known and unknown risks and uncertainties, many of which are beyond the Company’s control, and cannot be predicted or quantified and consequently, actual results may differ materially from those expressed or implied by such forward-looking statements. Such risks and uncertainties include, without limitation, risks related to the occurrence or timing of the RHB-105 (Talicia®) PDUFA action date, risks related to the commencement or timing of our clinical trials with RHB-104, RHB-204, RHB-102 (Bekinda®) and Yeliva®, risks related to meetings scheduled with the FDA, including with regard to RHB-104 for Crohn’s disease, risks relating to side effects associated with use of our therapeutic products, as well as risks and uncertainties associated with (i) the initiation, timing, progress and results of the Company’s research, manufacturing, preclinical studies, clinical trials, and other therapeutic candidate development efforts, and the timing of the commercial launch of its therapeutic candidates; (ii) the Company’s ability to advance its therapeutic candidates into clinical trials or to successfully complete its preclinical studies or clinical trials or the development of a commercial companion diagnostic for the detection of MAP; (iii) the extent and number of additional studies that the Company may be required to conduct and the Company’s receipt of regulatory approvals for its therapeutic candidates, and the timing of other regulatory filings, approvals and feedback; (iv) the manufacturing, clinical development, commercialization, and market acceptance of the Company’s therapeutic candidates; (v) the Company’s ability to successfully commercialize and promote Donnatal®, EnteraGam® and Mytesi®; (vi) the Company’s ability to establish and maintain corporate collaborations; (vii) the Company's ability to acquire products approved for marketing in the U.S. that achieve commercial success and build its own marketing and commercialization capabilities; (viii) the interpretation of the properties and characteristics of the Company’s therapeutic candidates and the results obtained with its therapeutic candidates in research, preclinical studies or clinical trials; (ix) the implementation of the Company’s business model, strategic plans for its business and therapeutic candidates; (x) the scope of protection the Company is able to establish and maintain for intellectual property rights covering its therapeutic candidates and its ability to operate its business without infringing the intellectual property rights of others; (xi) parties from whom the Company licenses its intellectual property defaulting in their obligations to the Company; (xii) estimates of the Company’s expenses, future revenues, capital requirements and needs for additional financing; (xiii) the effect of patients suffering adverse experiences using investigative drugs under the Company's Expanded Access Program; (xiv) competition from other companies and technologies within the Company’s industry; and (xv) the hiring and employment commencement date of executive managers. More detailed information about the Company and the risk factors that may affect the realization of forward-looking statements is set forth in the Company's filings with the Securities and Exchange Commission (SEC), including the Company's Annual Report on Form 20-F filed with the SEC on February 26, 2019, as amended on May 15, 2019. All forward-looking statements included in this press release are made only as of the date of this press release. The Company assumes no obligation to update any written or oral forward-looking statement, whether as a result of new information, future events or otherwise, unless required by law.

*Company contact:*
Adi Frish
Senior VP Business Development & Licensing
RedHill Biopharma
+972-54-6543-112
adi@redhillbio.com* IR contact (U.S.):*
Timothy McCarthy, CFA, MBA
Managing Director, Relationship Manager
LifeSci Advisors, LLC
+1-212-915-2564
tim@lifesciadvisors.com

1 Results were provided by independent third party prior to database lock and are not final






						RedHill Announces Full Results from MAP US Phase 3 Study and Supportive Top-Line Results from MAP US2 Study with  RHB-104 in Crohn’s Disease | 2019 | News | RedHill
					






					www.redhillbio.com


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## Crohn2357

*The Crohn’s Vaccine*


*Timelines are current best estimates and are not set in stone. Delays are commonplace in research due to the unpredictable nature of organising and running trials (last updated 09/10/2019).*
*Progress*
The Crohn’s MAP Vaccine is being developed and commercialized by hav-vaccines.com
It has been manufactured by scientists at the Jenner Institute, Oxford at their Clinical BioManufacturing Facility:
http://www.cbf.ox.ac.uk/cbf-collaboration-with-hav-vaccines-ltd-for-crohn-s-disease-vaccine 
Manufacture and Phase I trials have been funded by the company HAV Vaccines Ltd who own the intellectual property rights to the Vaccine.
HAV Vaccines Ltd are seeking further investment to complete funding for Phase IIa trials. Companies or individuals interested in investing should contact Mr Michael Stallibrass (Email: stalli@hav-vaccines.com) for more information.
*The Vaccine*
Prof. Hermon-Taylor, together with Dr Tim Bull and other members of the team at St George’s University of London and scientists at the Jenner Institute University of Oxford, developed a modern DNA vaccine against MAP. This took 10 years and cost around £850,000, much of it donated by the families of Crohn’s patients, without whom this new vaccine would not exist. The key features of the Vaccine are:

*Treatment*: Modern vaccines can be used to treat, as well as prevent, established chronic infectious diseases. If the vaccine works as well in humans as it does in cattle then there is every chance that it could CURE, or significantly attenuate, Crohn’s Disease. However, it may take time for inflammation to settle and the gut to heal after vaccination in people with longstanding Crohn’s. The vaccine would not be expected to reverse established scarring, such as strictures, at sites of previous active disease.
*Prevention*: The vaccine could be given to those at higher risk of developing Crohn’s Disease (e.g. children of those with Crohn’s) to prevent them from ever getting the disease. It could also be given to domestic livestock to prevent MAP getting into the food chain in the first place. Although this would not eradicate exposure completely (MAP still exists within the environment) it could dramatically reduce human exposure.
*Mechanism* of action: The vaccine is what is called a ‘T-cell’ vaccine. T-cells are a type of white blood cell -an important player in the immune system- in particular, for fighting against organisms that hide INSIDE the body’s cells –like MAP does. Many people are exposed to MAP but most don’t get Crohn’s –Why? Because their T-cells can ‘see’ and destroy MAP. In those who do get Crohn’s, the immune system has a ‘blind spot’ –their T-cells cannot see MAP. The vaccine works by UN-BLINDING the immune system to MAP, reversing the immune dysregulation and programming the body’s own T-cells to seek out and destroy cells containing MAP. For general information, there are two informative videos about T Cells and the immune system below.
*Efficacy*: In extensive tests in animals (in mice and in cattle), 2 shots of the vaccine spaced 8 weeks apart proved to be a powerful, long-lasting stimulant of immunity against MAP. To read the published data from the trial in mice, click here. To read the published data from the trial in cattle, click here.
*Safety*: There were no apparant adverse effects from the vaccine in either of the animal trials. Obviously the vaccine still needs to be tested in humans… but because it is highly specific, targeting only MAP and MAP-containing cells, we would predict that the safety profile in humans is likely to be very similar to that in animals.









						The Crohn's Vaccine - Crohn's MAP Vaccine
					

A modern therapeutic Crohn's Vaccine against Mycobacterium avium subspecies paratuberculosis (MAP). A trial in humans is needed to take the vaccine from lab to clinic.




					www.crohnsmapvaccine.com


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## Crohn2357

*King’s College London Thank-You Brochure*





President and Principal of King’s College London, Professor Edward Byrne, thanks everyone who has supported Crohn’s test research. In the booklet you can also read contributions from Professor Hermon-Taylor, Dr Amy Hermon-Taylor, Dr Gaurav Agrawal, Dr Paul Cross, Research Fellow Neil Rayment and fundraiser Christine Clifford.
KCL FSD THANK YOU BROCHURE – CROHNS 2019 – DIGITAL AW









						King's College London Thank-You Brochure - Crohn's MAP Vaccine
					

President and Principal of King’s College London, Professor Edward Byrne, thanks everyone who has supported Crohn’s test research. In the booklet you can also read contributions from Professor Hermon-Taylor, Dr Amy Hermon-Taylor, Dr Gaurav Agrawal, Dr Paul Cross, Research Fellow Neil Rayment and...




					www.crohnsmapvaccine.com


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## Crohn2357

*Antibiotic Add-On Active in Crohn's Disease*
*More evidence for a mycobacterial origin*
Charles Bankhead,October 31, 2019
SAN ANTONIO -- Treatment with an oral antibiotic combination led to clinically and significantly meaningful improvement in clinical response and remission in patients with active Crohn's disease, a randomized placebo-controlled trial showed.

Patients treated with antibiotics targeting _Mycobacterium avium paratuberculosis_ (MAP) had significantly higher rates of clinical remission and response at 26 weeks. Improvement occurred more often in patients taking concomitant anti-tumor necrosis factor (TNF) or immunosuppressive therapy.

A small subgroup analysis suggested the combination of rifabutin, clarithromycin, and clofazimine led to endoscopic healing, David Y. Graham, MD, of Baylor College of Medicine in Houston, reported here at the American College of Gastroenterology meeting.

"Antimicrobial therapy with RHB-104 demonstrated meaningful improvement in the efficacy and biomarkers of active inflammation and endoscopic recovery in patients with active Crohn's disease," said Graham. "The onset of symptomatic improvement was rapid and was seen by at least week 4. Clinical remission occurred as early as week 16 and was sustained through week 52. There was a trend toward corticosteroid-free remission at week 52."

"These data provide further evidence suggesting a role for _Mycobacterium avium paratuberculosis_, or a similar organism, in the pathogenesis of Crohn's disease," he added. "Remission data and safety data suggest this potentially may be a use of adjuvant therapy to other medications to enhance the response to medical therapy."

In the discussion that followed the presentation, an audience member inquired about the frequency of bacterial infection in Crohn's disease and the potential role of antibiotic therapy in treatment.

"This is either an additional therapy, or it's the beginning of a paradigm shift," Graham responded. "I see this as we're standing at the same place we were standing with Helicobacter 30 years ago, when the question was, have we found something that if we eradicate, would it change the natural history of the disease and cure it. This is going in that direction, but it certainly hasn't gotten there at this point."

*Infectious Link?*

In response to a question about the causative role of MAP in Crohn's disease and specificity of the antibiotic combination, Graham pointed out that a "tremendous number of other studies" of antibiotics for inflammatory bowel disease failed to demonstrate a clinically meaningful effect. The study is hypothesis generating, he added, and suggests "this is a potential cause and this is a potential treatment."

The bottom line is whether the treatment had an effect on the disease. "The answer unquestionably was yes. It's very positive data to pursue the hypothesis, but the answer is yet to come."

The association between Crohn's disease and infection with MAP dates back to the 1930s. MAP can be cultured from peripheral blood mononuclear cells of patients with Crohn's disease more often than in healthy controls, said Graham. The observations led to the hypothesis that treatment of Crohn's disease with anti-MAP therapy would support a causative role for MAP in Crohn's.

The hypothesis led to a global multicenter, randomized trial to evaluate the efficacy of RHB-104 in patients with moderately or severely active Crohn's disease. Eligibility criteria included diagnosed disease of the ileum and/or colon at least 6 months prior to randomization; active Crohn's disease confirmed by abnormal endoscopy, abnormal imaging, C-reactive protein level ≥1.0 mg/dL, or fecal calprotectin level ≥162.9 µg/g stool; and a Crohn's Disease Activity Index (CDAI) score of 220-450.

Eligible patients were already being treated with one or more medications for Crohn's disease: 5-ASA, corticosteroids, azathioprine, 6-mercaptopurine, methotrexate, infliximab (Remicade), or adalimumab (Humira).

The trial had a primary endpoint of clinical remission (CDAI <150) at week 26. Key secondary endpoints included clinical response (100-point decrease in CDAI) at week 26, clinical remission at weeks 16 and 52, durable remission, and corticosteroid-free remission.

*Key Findings*

Data analysis included 331 randomized patients who had a mean age of 39, and men accounted for 57% of the study population. Two thirds of the patients had the ileum as the primary disease site, and the time since diagnosis of Crohn's disease averaged 10.6 years. The mean baseline CDAI score was 296, and laboratory values included mean CRP of 1.36 mg/dL and calprotectin of 668 µg/g of stool. About half the patients were on corticosteroids and immunosuppressives, and a fifth were being treated with TNF inhibitors.

After 26 weeks of treatment, 36.7% of patients in the RHB-104 group had attained clinical remission as compared with 23.0% of the placebo group (_P_=0.007), and 44.0% versus 30.9% had clinical response (_P_=0.916). Additionally, 42.2% of the RHB-104 group achieved early remission (week 16) versus 29.1% of the placebo group (_P_=0.015).

Patients on concomitant anti-TNF therapy tended toward a greater absolute benefit (26-week remission rate of 35.5% vs 18.8%, _P_=0.08), but a significantly greater proportion of patients not treated with TNF inhibitors met the primary endpoint (37% vs 24.8%, _P_=0.03). Patients in the RHB-104 arm had significantly greater improvement in the abdominal pain and loose bowel movement components of the CDAI at weeks 16 and 20 and at week 24.

In a subgroup of 35 patients assessed endoscopically at 26 weeks, 35.7% of the RHB-104 group had at least 25% improvement in the Simple Endoscopic Score versus 9.5% for the placebo group (_P_=0.048), and 50% improvement was seen in 28.6% versus 4.8% of patients (_P_=0.11).

Significantly more patients in the RHB-104 group attained remission plus at least a 50% decrease in fecal calprotectin or CRP at weeks 16 (25.9% vs 9.7%, _P_=0.0002), 26 (21.1% vs 9.1%, _P_=0.003), and 52 (16.9% vs 7.9%, _P_=0.02). The proportion of patients with a calprotectin level ≥162.9 µg/g, decreased significantly through 52 weeks in the RHB-104 group as compared with the placebo group.

Durable remissions occurred significantly more often with RHB-104, including only visits at weeks 16 and 52 (25.3% vs 12.4%, _P_=0.003) and all visits from week 16 through week 52 (18.7% vs 8.5%, _P_=0.008).

In general, the type and frequency of adverse events were similar, Graham reported.

The study was supported by RedHill Biopharma.
Graham and several coinvestigators disclosed relationships with RedHill Biopharma, including employment.


*Primary Source
American College of Gastroenterology*
Source Reference: Graham DY, et al "RHB-104, a fixed-dose, oral antibiotic combination against Mycobacterium avium paratuberculosis (MAP) infection, is effective in moderately to severely active Crohn's disease" ACG 2019; Abstract 58.









						Antibiotic Add-On Active in Crohn's Disease
					

More evidence for a mycobacterial origin




					www.medpagetoday.com


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## kiny

If MAP was the sole offending agent, you would expect long term treatment with macrolides to be far more effective. That the treatment would take a long time is expected considering other mycobacterial infections like TB often require months of treatment too.

What isn't normal is that patients relapse on those macrolides. The studies are also not trying to detect MAP, and hide behind the idea that it's hard to culture. It is hard to culture, but if so many people with CD supposedly have MAP, where are all those ziehl-neelsen stains showing how the treatment is able to get rid of MAP.

I think the anti-MAP treatments just lower general bacterial load, resulting in an initial improvement in some patients, that is transient. It will potentially leave some patients worse off in the long term. Giving antibiotics that are completely ineffective against gram negative bacteria, for months, is going to give a fitness advantage to enterobacteriaceae like E coli when patients relapse.


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## kiny

Also, don't forget that macrolides don't just have an antibacterial effect, they also to have a mild anti-inflammatory effect. An initial improvement in some crohn's disease patients with a relapse might be attributed to the anti-inflammatory effect of the antibiotics. Giving the macrolides just for their anti-inflammatory effect would be crazy, they have far too many potential side effects for that.


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## Crohn2357

Human Paratuberculosis Foundation Quarterly Newsletter
October 2019



			https://humanpara.org/wp-content/uploads/2019/10/The-MAP-Gap-10-1-19.pdf


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## Crohn2357

October 2019 UPDATE: MAP/Crohn's Disease Testing Study | Human Paratuberculosis Foundation
					

Human Para's inaugural MAP testing study of 201 blinded samples is nearing completion. Read about our progress, DNA testing, and when results will be published!




					humanpara.org


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## Crohn2357

*A Message from Professor Hermon-Taylor*


> ...
> 
> As with so many things, covid-19 is having a major impact on research. At the point at which the pandemic struck, our Phase II vaccine trial was set up and awaiting the final local authorisations to begin. However, all clinical research not directly related to coronavirus has now been paused. This is because taking part in a trial would put patients at risk of catching covid-19, due to the travel involved as well as the inability to maintain social distancing during appointments. Similarly, all laboratory research not related to coronavirus is also on hold (due to the risk of spreading the virus with staff travelling to and from work) and King’s College London is closed. Hence work on our MAP test is currently paused too. We will be ready to go as soon as social distancing requirements are relaxed and permission is given for non-covid related clinical trials to restart and labs to re-open.
> I would like to thank all our wonderful supporters for your continuing support during this very difficult time.
> 
> Posted on April 17, 2020 by admin1











						A Message from Professor Hermon-Taylor - Crohn's MAP Vaccine
					

I wanted to bring you an update and send my best wishes in these unprecedented times. I expect it may have been a very difficult Easter for many of you, being unable to spend time with family and friends and struggling with all the hardships and uncertainties this pandemic has brought. My...




					www.crohnsmapvaccine.com


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## Crohn2357

*Putting Crohn's on the MAP: Five Common Questions on the Contribution of Mycobacterium avium subspecies paratuberculosis to the Pathophysiology of Crohn's Disease*
Gaurav Agrawal 1 2, John Aitken 3, Harrison Hamblin 4, Michael Collins 5, Thomas J Borody 4

*Abstract*
For decades, Mycobacterium avium subspecies paratuberculosis (MAP) has been linked to the pathogenesis of Crohn's disease. Despite many investigations and research efforts, there remains no clear unifying explanation of its pathogenicity to humans. Proponents argue Crohn's disease shares many identical features with a granulomatous infection in ruminants termed Johne's disease and similarities with ileo-cecal tuberculosis. Both are caused by species within the Mycobacterium genus. Sceptics assert that since MAP is found in individuals diagnosed with Crohn's disease as well as in healthy population controls, any association with CD is coincidental. This view is supported by the uncertain response of patients to antimicrobial therapy. This report aims to address the controversial aspects of this proposition with information and knowledge gathered from several disciplines, including microbiology and veterinary medicine. The authors hope that this discussion will stimulate further research aimed at confirming or refuting the contribution of MAP to the pathogenesis of Crohn's disease and ultimately lead to advanced targeted clinical therapies.
*Keywords: *Antibiotic treatment for Crohn's disease; Crohn's disease; Mycobacteria PCR; Mycobacterium avium paratuberculosis; Tuberculosis treatment.

Agrawal G, Aitken J, Hamblin H, Collins M, Borody TJ. Putting Crohn's on the MAP: Five Common Questions on the Contribution of Mycobacterium avium subspecies paratuberculosis to the Pathophysiology of Crohn's Disease. Dig Dis Sci. 2020 Oct 22:1–11. doi: 10.1007/s10620-020-06653-0. Epub ahead of print. PMID: 33089484; PMCID: PMC7577843.



			https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577843/pdf/10620_2020_Article_6653.pdf


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## Crohn2357

*Anti-MAP Triple Therapy Supports Immunomodulatory 






			Therapeutic Response in Crohn’s Disease through Downregulation of NF-κB Activation in the Absence of MAP Detection
		
Click to expand...

*


> We are delighted to share a new paper from Naser et al, showing that several antibiotics have demonstrated anti-inflammatory effects that are independent of their antibacterial properties. They show that anti-MAP triple antibiotics combination (RHB-104) exhibits anti-inflammatory and immunomodulatory activity alongside its known synergistic bactericidal activity against MAP infection. Very encouraging news! Thanks to Ahmad Qasem for sharing with us this latest piece of the MAP puzzle.
> Click here to read the full paper.
> 
> 
> 
> 
> 
> 
> Posted on November 19, 2020 by admin1











						Anti-MAP Triple Therapy Supports Immunomodulatory Therapeutic Response in Crohn’s Disease through Downregulation of NF-κB Activation in the Absence of MAP Detection - Crohn's MAP Vaccine
					

We are delighted to share a new paper from Naser et al, showing that several antibiotics have demonstrated anti-inflammatory effects that are independent of their antibacterial properties. They show that anti-MAP triple antibiotics combination (RHB-104) exhibits anti-inflammatory and...




					www.crohnsmapvaccine.com


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## irishgal

New study about antibiotic susceptibility of human and animal MAP strains beginning in January 2021. Very excited that essential oils will be considered too!
https://humanpara.org/what-is-the-susceptibility-of-map-strains-to-antibiotic-combinations/


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## Crohn2357

Our March Newsletter is out! - Crohn's MAP Vaccine
					

Please click here to view the latest news about the trial, the MAP test and our fundraising efforts.




					crohnsmapvaccine.com


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## Crohn2357

Q & A with vaccinologist Dr Tom Merritt on viral vector vaccines - including the current Covid vaccine from Astra Zeneca. - Crohn's MAP Vaccine
					

What follows is a transcript of the Q&A session which took place on World MAP Day, 15th March 2021. This was a Facebook event which remains accessible on our main Facebook page. We are placing it here to reach a wider audience. Sincere thanks to Dr Tom Merritt for answering some very difficult...




					crohnsmapvaccine.com


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## Crohn2357

*



			Crohn’s MAP Vaccine booster shot proven safe
		
Click to expand...

*


> At last, the paper we have been waiting for!
> 
> 
> ABSTRACT: Heterologous prime-boost strategies are known to substantially increase immune responses in viral vectored vaccines. Here we report on safety and immunogenicity of the poxvirus Modified Vaccinia Ankara (MVA) vectored vaccine expressing four Mycobacterium avium subspecies paratuberculosis antigens as a single dose or as a booster vaccine following a simian adenovirus (ChAdOx2) prime. We demonstrate that a heterologous prime-boost schedule is well tolerated and induced T-cell immune responses.
> 
> Full paper from Gilbert et al here.
> Posted on March 30, 2021 by admin1











						Crohn's MAP Vaccine booster shot proven safe - Crohn's MAP Vaccine
					

At last, the paper we have been waiting for! ABSTRACT: Heterologous prime-boost strategies are known to substantially increase immune responses in viral vectored vaccines. Here we report on safety and immunogenicity of the poxvirus Modified Vaccinia Ankara (MVA) vectored vaccine expressing four...




					crohnsmapvaccine.com


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## Crohn2357

The first Crohn's patient receives the Crohn's MAP Vaccine - Crohn's MAP Vaccine
					

We are delighted to announce that the first Crohn’s patient has now received the Crohn’s MAP Vaccine. It’s an emotional day! This is Sean Young’s story… “So, a crazy thing happened this week. First, though, a bit of background… I started my Crohn’s journey many years ago. I didn’t know I had...




					crohnsmapvaccine.com


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## Crohn2357

Obituary for Professor John Hermon-Taylor - Crohn's MAP Vaccine
					

It is with great sadness that we share The Telegraph obituary for our beloved professor. The Times also shared an obituary on 18th November. A memorial service will take place in Wimbledon this Friday 3rd Dec at 12 noon and will be open to anyone who would like to attend. There is also a zoom…...




					crohnsmapvaccine.com


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## kiny

I'm so sorry to hear that, hope he is in peace.


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## Crohn2357

IBD research at Lancaster University - Crohn's MAP Vaccine
					

Could you help MAP research by taking part in this short survey? It is looking at the epidemiology of IBD in the U.K. and whether living in areas with a number of geographical influences, including high levels of MAP exposure, increases your chances of getting IBD. The survey is open to patients...




					crohnsmapvaccine.com


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## Crohn2357

Delta_hippo said:


> Just to update folk the guy who was the first Crohn’s patient to receive a low dose of the anti map vaccine has posted an update in Facebook.  He says he is only one person and cannot draw any conclusions yet but he is now averaging 2 BMs a day and getting to the loo in time which is better than before and this has lasted a few months.


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## kiny

Development and Validation of Anti-paratuberculosis-nocardia Polypeptide Antibody [Anti-pTNP] for the Diagnosis of Crohn’s Disease
					

AbstractBackground and Aims. Non-invasive biomarkers in sera of patients with inflammatory bowel disease [IBD] are not currently available for rapidly and accur




					academic.oup.com


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## Crohn2357

"Trial update and a call for volunteers!"


__ https://twitter.com/i/web/status/1493530609565802498


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## Poppysocks

How do you find a doctor who will prescribe anti map therapy?


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## Crohn2357

Poppysocks said:


> How do you find a doctor who will prescribe anti map therapy?



MAP Specialists

MAP Doctors and Research Centers Around the Globe

E-mail Human Paratubetculosis Foundation. They will most likely help. Also use various Crohn’s Map Facebook groups.


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## Crohn2357

Open AccessObituary
*Hermon-Taylor: M. paratuberculosis and Crohn’s Disease—The Book of Revelation According to John *
by
Coad Thomas Dow



McPherson Eye Research Institute, University of Wisconsin, 9431 WIMR, 1111 Highland Avenue, Madison, WI 53705, USA
Pathogens 2021, 10(11), 1469; https://doi.org/10.3390/pathogens10111469
Received: 1 November 2021 /Accepted: 10 November 2021 /Published: 12 November 2021
(This article belongs to the Special Issue Role of Pathogens in Chronic Inflammatory Diseases and Cancer)
Download PDF Citation Export

Professor John Hermon-Taylor recently passed away on 16 October 2021. Prof. Hermon-Taylor was born in 1936, he received his B.A. degree in 1957 and his M.B. degree in 1960 from the Cambridge University. This London physician–scientist was an early elucidator of the zoonotic capacity of Mycobacterium avium ss. paratuberculosis (MAP). In 1998, John Hermon-Taylor (JHT) published an article in the British Medical Journal, a case report that featured a boy who, at seven years old, had cervical lymphadenitis. Five years later, when the same child presented with early Crohn’s disease, the archived lymphadenitis tissue was tested for MAP. It was positive, and the child was successfully treated with surgery followed by anti-mycobacterial drugs rifabutin and clarithromycin [1]. JHT’s work and advocacy continued to link MAP to Crohn’s disease [2] and he emphasized that, while humans are broadly exposed to MAP in dairy products, they are secondarily exposed to environmental MAP [3]. He predicted increasing MAP-related human disease with his “doomsday” article, a notably prescient forecast [4].





JHT’s easy manner and approachability encouraged many scientists to explore MAP’s contribution not only to Crohn’s disease, but to several other inflammatory and autoimmune diseases. Largely due to his foundational contributions, MAP scientists from around the world generated a 2017 consensus article that emphasized the zoonotic impact of MAP on human health [5].
Though the link of MAP zoonosis to Crohn’s disease has been a medical controversy for over one hundred years [6], validation of JHT’s effort has come from numerous recent studies showing Crohn’s disease resolution with anti-mycobacterial therapy targeted against MAP [7,8,9,10]. Moreover, MAP is now linked to an increasing list of inflammatory and autoimmune diseases [11]. To date, MAP has been causally associated with granulomatous diseases besides Crohn’s: sarcoidosis [12,13] and Blau syndrome [14]. Through molecular mimicry from mycobacterial protein elements, MAP is found to induce autoantibodies in autoimmune diabetes (T1D) [15], multiple sclerosis [16], autoimmune thyroiditis [17], lupus [18] and rheumatoid arthritis [19,20].
This writer predicts that, in the future, JHT’s contributions will be acknowledged throughout the world, perhaps securing him a commemorative place in Kensington Gardens beside the likes of Edward Jenner.
*References*

Hermon-Taylor, J.; Barnes, N.; Clarke, C.; Finlayson, C. Mycobacterium paratuberculosis cervical lymphadenitis, followed five years later by terminal ileitis similar to Crohn’s disease. BMJ 1998, 316, 449–453. [Google Scholar] [CrossRef] [PubMed]
Bull, T.J.; McMinn, E.J.; Sidi-Boumedine, K.; Skull, A.; Durkin, D.; Neild, P.; Rhodes, G.; Pickup, R.; Hermon-Taylor, J. Detection and verification of Mycobacterium avium subsp. paratuberculosis in fresh ileocolonic mucosal biopsy specimens from individuals with and without Crohn’s disease. J. Clin. Microbiol.2003, 41, 2915–2923. [Google Scholar] [CrossRef] [PubMed]
Pickup, R.W.; Rhodes, G.; Arnott, S.; Sidi-Boumedine, K.; Bull, T.J.; Weightman, A.; Hurley, M.; Hermon-Taylor, J. Mycobacterium avium subsp. paratuberculosis in the catchment area and water of the River Taff in South Wales, United Kingdom, and its potential relationship to clustering of Crohn’s disease cases in the city of Cardiff. Appl. Environ. Microbiol. 2005, 71, 2130–2139. [Google Scholar] [CrossRef] [PubMed]
Hermon-Taylor, J. Mycobacterium avium subspecies paratuberculosis, Crohn’s disease and the Doomsday scenario. Gut Pathog.2009, 1, 15. [Google Scholar] [CrossRef] [PubMed]
Kuenstner, J.T.; Naser, S.; Chamberlin, W.; Borody, T.; Graham, D.Y.; McNees, A.; Hermon-Taylor, J.; Hermon-Taylor, A.; Dow, C.T.; Thayer, W.; et al. The Consensus from the Mycobacterium avium ssp. paratuberculosis (MAP) Conference 2017. Front. Public Health 2017, 5, 208. [Google Scholar] [CrossRef] [PubMed]
Sechi, L.A.; Dow, C.T. Mycobacterium avium ss. paratuberculosis zoonosis-The hundred Year War-Beyond Crohn’s disease. Front. Immunol. 2015, 6, 96. [Google Scholar] [CrossRef] [PubMed]
Ekundayo, T.C.; Okoh, A.I. Systematic assessment of Mycobacterium aviumsubspecies Paratuberculosis infections from 1911–2019: A growth analysis of association with human autoimmune diseases. Microorganisms 2020, 8, 1212. [Google Scholar] [CrossRef] [PubMed]
Agrawal, G.; Clancy, A.; Huynh, R.; Borody, T. Profound remission in Crohn’s disease requiring no further treatment for 3–23 years: A case series. Gut Pathog. 2020, 12, 16. [Google Scholar] [CrossRef] [PubMed]
Borody, T.J.; Bilkey, S.; Wettstein, A.R.; Leis, S.; Pang, G.; Tye, S. Anti-mycobacterial therapy in Crohn’s disease heals mucosa with longitudinal scars. Dig. Liver Dis. 2007, 39, 438–444. [Google Scholar] [CrossRef] [PubMed]
Savarino, E.; Bertani, L.; Ceccarelli, L.; Bodini, G.; Zingone, F.; Buda, A.; Facchin, S.; Lorenzon, G.; Marchi, S.; Marabotto, E.; et al. Antimicrobial treatment with the fixed-dose antibiotic combination RHB-104 for Mycobacterium avium subspecies paratuberculosis in Crohn’s disease: Pharmacological and clinical implications. Expert. Opin. Biol. Ther. 2019, 19, 79–88. [Google Scholar] [CrossRef] [PubMed]
Dow, C.T.; Sechi, L.A. Cows get Crohn’s disease and they’re giving us diabetes. Microorganisms 2019, 7, 466. [Google Scholar] [CrossRef] [PubMed]
Celler, B.G. Case Study: Cardiac sarcoidosis resolved with Mycobacterium avium paratuberculosis antibiotics (MAP). Sarcoidosis Vasc. Diffus. Lung Dis. 2018, 35, 171–177. [Google Scholar]
Reid, J.D.; Chiodini, R.J. Serologic reactivity against Mycobacterium paratuberculosis antigens in patients with sarcoidosis. Sarcoidosis 1993, 10, 32–35. [Google Scholar] [PubMed]
Dow, C.T.; Ellingson, J.L. Detection of Mycobacterium avium ss. Paratuberculosis in blau syndrome tissues. Autoimmune Dis.2010, 2011, 127692. [Google Scholar] [PubMed]
Noli, M.; Meloni, G.; Manca, P.; Cossu, D.; Palermo, M.; Sechi, L.A. HERV-W and Mycobacteriumavium subspecies paratuberculosis are at play in pediatric patients at onset of type 1 diabetes. Pathogens2021, 10, 1135. [Google Scholar] [CrossRef] [PubMed]
Cossu, D.; Masala, S.; Sechi, L.A. A Sardinian map for multiple sclerosis. Future Microbiol.2013, 8, 223–232. [Google Scholar] [CrossRef] [PubMed]
Sisto, M.; Cucci, L.; D’Amore, M.; Dow, T.C.; Mitolo, V.; Lisi, S. Proposing a Relationship Between Mycobacterium Avium Subspecies Paratuberculosis Infection and Hashimoto’s Thyroiditis. Scand. J. Infect. Dis. 2010, 42, 787–790. [Google Scholar] [CrossRef] [PubMed]
Dow, C.T. Detection of M. Paratuberculosis Bacteremia in a child with lupus erythematosus and Sjogren’s syndrome. Autoimmun Infect. Dis. 2016, 2, 2470-1025. [Google Scholar] [CrossRef]
Bo, M.; Erre, G.L.; Bach, H.; Slavin, Y.N.; Manchia, P.A.; Passiu, G.; Sechi, L.A. PtpA and PknG Proteins Secreted by Mycobacterium avium subsp. paratuberculosisare recognized by sera from patients with rheumatoid arthritis: A case-control study. J. Inflamm. Res. 2019, 12, 301–308. [Google Scholar] [PubMed]
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To finish our series of  #worldmapday posts, we are sharing a recent and rather beautiful paper on Professor John Hermon-Taylor. "The Revelation According to John."  Dow predicts that in the future, JHT’s contributions will be acknowledged throughout the world, perhaps securing him a commemorative place in Kensington Gardens beside the likes of Edward Jenner. Wouldn't that be wonderful.

#crohns









						Hermon-Taylor: M. paratuberculosis and Crohn’s Disease—The Book of Revelation According to John
					

Professor John Hermon-Taylor recently passed away on 16 October 2021 [...]




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## Crohn2357

From CMV’s FB Group:

“Many members of this group have been with us for 7+ years through all of the fundraising, setbacks, fears, and tears, and sadly some members are no longer with us.
For those that are, we are now only just over a month away from the end of the phase 1b and six months from the intention to publish date, we are so near to finding out if Crohns could really be a disease of the past, if MAP bacteria does cause Crohn’s disease in susceptible people and if the rapid  MAP test really does work as well as it seems to.
For safety of the trials, information is never to our knowledge shared during any research trial phases. Confidentiality of volunteers is paramount, although volunteers are free to share any part of their journey if they should choose to as a couple have earlier, however many prefer to remain private or may not be a member of this group.
You can rest assured Dr Amy Hermon-Taylor will post any updates, just as soon as she has anything to report.”


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