# RHB104 - Let's pray together ...



## worriedboy (Oct 15, 2013)

http://finance.yahoo.com/news/redhill-biopharmas-rhb-104-combination-110000493.html


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## nogutsnoglory (Oct 15, 2013)

Very promising! We need good news after the whipworm trial failed.


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## Malgrave (Oct 16, 2013)

Thank you very much! I really believe in this drug!

Last summer the biopsies from my 5 year old son showed an atypical mycobacterium infection in his intestines. Immediately the doctorrs wanted him to start Clarithromycin and Rifampicin (I have heard that the main antibiotics behind RHB104 might be clarithromycin, clofazimine and rifabutin... Does anybody know?). After 2 months his condition was clearly improved and the inflammation in his intestines had decreased considerably. "Unfortunately" the result of the cultivation of the bacteria was negative and the antibiotics were stopped. After that his condition has gone worse again.

I will certainly raise this issue again when we meet the doctors next time.


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## Malgrave (Oct 16, 2013)

Here is a bit more about the drug:

http://biotuesdays.com/2013/08/13/redhill-readying-phase-3-trials-in-crohns/


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## Malgrave (Oct 16, 2013)

Can anybody tell me what does _Orphan Drug Designation _ mean?

Thanks!


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## kiny (Nov 5, 2013)

Malgrave said:


> I have heard that the main antibiotics behind RHB104 might be clarithromycin, clofazimine and rifabutin... Does anybody know?


that's right, it's because they're intracellular and macrophage penetrating

MAP and AIEC replicate inside macorphages as trojan horses

NOD2, ATG16L1 and IL23 abonormalies impacts handling of intracellular bacteria, specifically autophagy and macrophage competence, what people refer to as innate immunodeficiency in crohn's disease

macrophages populate the digestive tract in huge numbers, if they get activated they become potential APC, antigen presenting cells for the lymph system, which activates lymphocytes and results in non-stop inflammation if the macrophage isn't capable of dealing with the bacteria

antibiotics are severely underused in crohn's disease

partly because there's no money in them and partly GI ignorance


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## kiny (Nov 5, 2013)

Malgrave said:


> Can anybody tell me what does _Orphan Drug Designation _ mean?
> 
> Thanks!


it's a status a drug gets in the form of subsidising or patent protection or tax benefits, sometimes they also get help getting approved faster

it's used for uncommon and chronic diseases. "orphan diseases", so there is incentive for companies or institutions to develop new medication, otherwise those diseases might be ignored because they're too rare to put money in them


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## Coco Jambo (Nov 8, 2013)

Is the exact amount of the specific antibiotics known? Is it possible to try it on my own (supervised by my GI)?


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## kiny (Nov 8, 2013)

Don't know what the exact mg are, it's probably 250 or 500mg for those. There's negatives just like with any drug. While these antibiotics are relatively safe, antibiotics create resistance. Also, one of those antibiotics is used to treat people with TB and some other infections, which isn't a good thing when you're on antibiotics for so long.

You should ask your GI, antibiotics are a viable treatment when other medication has failed.

Also, this is about crohn's disease, antibiotics aren't effective for UC afaik.

.
Another small point is that let's say that this combo works, because a small study of 10 children isn't conclusive, that doesn't mean MAP is the cause or even relevant to this diseasse. It's just as likely that it targets another pathogen, and I know that if it does work, some people will say it's because one of those antibiotics is also mildly anti-inflammatory, but it's not enough to put 8 out of 10 kids in remission I'm sure. It's just a small study, it's meaningless on it's own really.

But that bacteria are directly related to crohn's disease isn't open for discussion anymore, all genetic predispositions in crohn's disease are related to bacterial handling, they all point to innate immunodeficiency.

There's only a few hypotheses that still make sense to me:

-persistent pathogen
-loss of tolerance towards commensal bacteria, which is a bit hard to explain because crohn's disease has skip lesions
-some immune response against a microparticle of unknown origin


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## Malgrave (Nov 25, 2013)

RedHill: First Patient Dosed In Phase III Trial Of RHB-104 For Crohn's disease:

http://www.nasdaq.com/article/redhi...-of-rhb-104-for-crohns-disease-20131125-00367


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## sir.clausin (Nov 25, 2013)

Interesting, people still think it´s MAP and some don´t. What if MAP one of the root causes, what says that people with crohns can´t be re-infected with the bug and get the same problem all over. We can´t take the antibiotics for life...


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## rollinstone (Nov 25, 2013)

If you get re-infected you go back on the anti-biotics, the whole point of the combination of 3 drugs is so that the pathogen (be it MAP or something else) cant become resistant.


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## kiny (Nov 25, 2013)

You also can't just avoid MAP unless you go on something like EN, MAP is obviously not only in milk, it's in red meat too, in other dairy products, etc.


When that cow gets sick with paratuberculosis, it's going to infect the rest of the herd.

A farmer has 2 choices at that point:

*tell authorities to take the animal away, which in the West means they lost a really expensive animal (In Japan they get a reward for it, which is why Japan has low Ptb)

*make hamburgers out of the cow

Take a wild guess what most farmers are doing.

Because tests of MAP aren't 100% reliable, they can get away with claiming they didn't know the animal was sick.


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## rollinstone (Nov 25, 2013)

Kiny, what are your thoughts in regards to MAP and colonic cd?


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## kiny (Nov 26, 2013)

Don't have any idea about it to be honest. 

In ruminants MAP goes for the ileum, it is extremely specific. In some animals it goes to the head like in pigs. 

What I do wonder sometimes is if colonic CD or crohn's collitis is the same disease as people with ileal crohn's disease, because there are no peyer's patches in the colon, only in the ileum, and the first signs of ileal crohn's disease is inflammation of the peyer's patches.


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## ellie (Nov 26, 2013)

Kiny, I've been wondering for some time whether they are in fact the same disease as well - I'm a Crohn's colitis diagnosis, with onset in my early 50's. Interestingly, for 2-3 years before that I had multiple, repeated episodes of sinusitis, assorted respiratory infections that were hard to shift and were treated with MANY antibiotics, often 2-3 courses.
Since the CD diagnosis 3 years ago I almost never get an URTI, and haven't needed any antibiotics (am only taking sulfasalazine, no immunosuppressant Rx)
Almost like there's been some sort of "gear shift" in my immune system...


 HD


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## sir.clausin (Nov 26, 2013)

There might just be a coicidence, but I know at least six people personally, who developed crohns later in their teens after being treated with lots of antibiotics for *earinfection*.

Ear infection of everthing....is there special antibiotics they usually prescripe for that which could be the common cause?


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## ellie (Nov 26, 2013)

My impression is that the major culprits are tetracyclines (often prolonged, maybe low dose) for acne or other indications, and Augmentin -amoxicillin + claevulinic acid 


 HD


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## sir.clausin (Nov 26, 2013)

I ate tetracykline for 6months for my acne.

Do I need to say that It came back with a vengence


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## rollinstone (Nov 26, 2013)

I was on doxycycline for years, then came the onset of crohns, im hoping to take legal action as more and more evidence piles up showing the association as irrefutable


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## wildbill_52280 (Nov 26, 2013)

Joshuaaa said:


> I was on doxycycline for years, then came the onset of crohns, im hoping to take legal action as more and more evidence piles up showing the association as irrefutable


i was thinking to myself how would we prove conclusively(with scientific observations) that doxycycline or any other antibiotic can cause IBD? when right now we have lots of evidence that suggests,  that it cannot lead to crohns or IBD in every case, yet simultaneously we have statistics that show it is actually a risk factor.

The best evidence we have to date that i have found is the studies that demonstrate a characteristic lack of diversity in clostridia cluster of bacteria which are important for regulating inflammation, and a study done on antibiotic associated diarrhea the showed augmentin/ amoxiclillin-clavulanic acid can severely suppress the growth of these bacteria, making a strong argument that suggests, some antibiotics are strong enough to affect these important groups of good bacteria, and it is highly probable, they can cause IBD.

 i have yet to speak to an attorney about all this, but i plan to show them all the latest scientific findings to see if they would be good enough to construct a legal case. we actually might have enough information here, and now with fecal transplant studys about to be completed, this would probably now be a smoking gun in the missing bacteria theory as the sole cause of IBD. after we have that evidence, it will be a very quick and successful court case i believe. that is all highly probable evidence though, not absolutely conclusive, but excellent. 

absolutely conclusive evidence, i'm not sure we could ever demonstrate that, but how about, the most probable explanation beyond all reason. we have to actually try to give someone IBD with an antibiotic, a low fiber diet and a vitamin d deficit, then cure them with a fecal transplant to provide absolute conclusive evidence. im sure not many people will volunteer for that study, making absolute conclusive evidence, impossible.


more info on fecal transplants-
http://www.crohnsforum.com/showthread.php?t=52400


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## sir.clausin (Nov 26, 2013)

Hah! Funny you should mentioned that wildbill. Check it
http://mobile.nutraingredients.com/Regulation/Japanese-firm-seeks-EU-probiotic-approval#.UpVoM9G9Kc0

I have already made an order for the probiotics with clostridia from Japan


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## rollinstone (Nov 26, 2013)

I'm in a similar boat wildbill, I am wanting to seek legal action, hopefully in the future we can, I just find it too much of a coinicidence that there are so many people w cd that have had problems after long term anti-biotic use


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## wildbill_52280 (Nov 27, 2013)

sir.clausin said:


> Hah! Funny you should mentioned that wildbill. Check it
> http://mobile.nutraingredients.com/Regulation/Japanese-firm-seeks-EU-probiotic-approval#.UpVoM9G9Kc0
> 
> I have already made an order for the probiotics with clostridia from Japan


believe it or not i was already aware of this strain being sold in the uk, and considered ordering it but never did. specifically for its ability to produce butyrate. i totally forgot about it though until you mentioned it. bacteria is classified as food and i dont even think they can be patented at all. unique processes to cultivate them may be patentable though. 

im pretty sure this was the brand too-

http://www.bayho.com/p/3708999.html?gclid=CKmPh5O9hLsCFfBDMgodjXkA8g

the bacterial count is very low though, buts still its cool that they have something on the market. id like to see the counts in the tens of billions, since there are 100 trillion and these may make up like 10% of that. rough guess of course tho.

if there is any probiotic that may help IBD, its this one.

at one time i considered trying to figure out how to isolate them cultivate them freeze dry them and sell them, as i may be able to do that easily, well i mean it seemed to be legal, but i dont have the experience or training, if probiotic bacteria is still regulated as a food product, but, i would not be able to advertise it for treating crohns due to the laws on health claims, unless we conducted a study and proved it put crohn's in remission/cured it. I'm not sure anything about this is patentable to any degree, therefore, large pharma profit potental isn't there, but of course you would make money, just not in the hundreds of millions, and there nothing to stop someone else from copying your business model, beyond a trademarked brand name.

there seem to be plenty of companies already working on all this stuff though, like rebiotix and maybe 2 more.


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