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BCG vaccine to treat autoimmune diseases such as type 1 diabetes, Crohn's, etc

Saw the other week information on the BCG vaccine used against TB, and how it is in clinical trials to see if it can cure many of type 1 diabetes. (The idea has worked in mice studies) Some write they believe Dr. Denise Faustman has found a cure for type 1 diabetes using the vaccine.

When going to her web sight I saw she thought potentially her idea could be used to treat Crohn's disease along with other autoimmune conditions such as MS.

Don't know if helpful or not but in case it might be of interest to others thought to post information.

Dr. Faustman's web sight can be viewed here:

http://faustmanlab.org

There are several YouTube videos on her work. One of them ~

https://www.youtube.com/watch?v=IRXbUtghP9Y
 

Trysha

Moderator
Staff member
Thank you for posting this information.
It would be interesting to know the mechanism by which this microbiological vaccine can be used in a non infection environment.
Where is the logic behind this approach and what is it that activated the researcher to go beyond the microbial application.
 
Interesting! I had the BCG at school, I was around 12/13 years old and I was one of the last school years to have it done routinely in the UK before it was phased out, due to the disease being considered eradicated.

I was diagnosed with Crohn’s at 24 but had symptoms for around 5 or 6 years. This August I was told I needed to go on Infliximab so I went for the blood screening to rule out anything nasty, and it turns out I have latent TB.

I’m 3 weeks in to a 3 month course of antibiotics to treat the underlying bug before they will start the Infliximab.

I’m assuming that I actually developed Crohn’s several years after being given the BCG, although I did have bouts of severe fatigue, lethargy and Anaemia as an early teen, these never came to anything and resolved for several years before the classic symptoms started.

I would be interested to see how I fit in to this theory? Did the BCG fail in my case?

It will be interesting to see how this one pans out!
 
Good questions. Basically I believe the doctor uses the vaccine differently than how it has been traditionally used. To better explain how the theories goes, there is a long FAQ section on her labs web sight. Many questions can be answered there.

Some of the answers she gives has this to mention about how it works ~

http://faustmanlab.org/research/faq.html

1. What were the Faustman Lab’s discoveries in end-stage diabetic mice that led to the current clinical trial program?
In 2001 (1) and in 2003 (2), the results of the Faustman lab's experiments in end-stage diabetic mice were published. The results showed that a brief, 40-day treatment selectively eliminated the disease-causing white blood cells in mice. This treatment killed only the cells that were causing the autoimmune destruction of the pancreas, and not healthy cells. These experiments also uncovered the ability of the pancreatic islets to regenerate on their own once the autoimmune destruction was stopped. In addition, the research team identified a new source of adult stem cells--adult stem cells in the spleen--that could form new islets in the formerly diabetic animals.

The Faustman Lab has also performed research using human blood samples and shown that humans with type 1 diabetes have disease-causing T cells that are similar to those found in diabetic mice (3). Based on this finding, they hypothesized that using a therapeutic approach in humans similar to the approach that reversed diabetes in mice might be effective. The BCG Human Clinical Trial Program is testing one part of this approach.
&

1. What is an autoimmune disease?
An autoimmune disease is a disease in which the immune system mistakenly attacks the body’s own tissues and cells. Type 1 diabetes is an autoimmune disease in which the insulin-producing cells of the pancreas are the target of the immune attack. Other autoimmune diseases include lupus, Crohn's disease, multiple sclerosis, scleroderma, Sjögren’s syndrome, and rheumatoid arthritis.

2. What is type 1 diabetes?
Type 1 diabetes is a chronic autoimmune disease. In type 1 diabetes, the immune system attacks the healthy insulin-producing beta cells of the pancreas. When this happens, the body is no longer able to produce enough insulin to regulate blood sugar levels which can lead to serious, life-threatening consequences. Approximately 1 million Americans have type 1 diabetes, many of whom are young children.

3. Why are you using BCG?
There is ample data to support the use of BCG in the human diabetes trials. BCG was used many years ago in early-stage diabetic mice and prevented diabetes. Unfortunately, many compounds work in early-stage NOD mice, but do not work in late-stage diabetic mice or in humans with advanced disease. BCG was also tried in the past in humans with new onset diabetes, prior to the knowledge of how BCG actually works in the body. In the human studies, some diabetic patients achieved remission with a single dose of BCG (Shehadeh et al. Lancet 1994), but two subsequent studies with a single dose of BCG showed no benefit.

Compared to when many previous BCG trials were conducted over a decade ago, the way BCG induces one's own TNF to change disease is now mapped in animal models and in some human diseases. This allows for thoughtful translation of this intervention to a human trial. We think these early trials of BCG in humans, although encouraging, could not be advanced until we understood BCG's mechanism of action (what it does) and had a way to monitor the drug's effect in the blood. Think about this: If we did not know that insulin regulated blood sugars, and if we did not know how to measure blood sugar, how could we tell whether insulin actually worked to help diabetics? In many ways, early BCG trials can be seen as similar to injecting insulin without knowing what it really does or how to measure its effects. One of our major laboratory efforts was to create a method to rapidly and precisely count the disease-causing cells in human blood and to use this test to evaluate whether BCG can eliminate these cells, and at what dose.

Only by completing clinical trials will we know if BCG will work to eliminate one population of disease-causing cells in human type 1 diabetes and be an effective treatment for people with long-term disease. We chose to test BCG because the agent is readily available and it works in humans in a similar way as the agent we successfully used in the mouse (CFA): BCG induces TNF, leading to the destruction of disease-causing T cells.

4. I am from outside the US and BCG is a routine vaccine in my country; why do I have type 1 diabetes?
BCG is used in some countries outside of the US as a vaccine to prevent tuberculosis, often given just once. Current evidence suggests that type 1 diabetes prevention or reversal requires repeated vaccination. In our type 1 diabetes reversal trials, we are testing BCG at different doses and schedules to identify the “optimal” regimen.
 
This is interesting news, thanks for sharing. Especially the fact that a Mycobactrium vaccine has shown potential. There is other research going on into Mycobacterium Avium ssp. Paratuberculosis (MAP) as an infectious, causative agent in Crohn's disease (CD) that finds the same thing. Also, several peer-reviewed research papers have described a link between MAP and Type 1 Diabetes.
In order to be an autoimmune condition, anti-bodies against the body's own cells have to be present. That is not the case in CD, and so focus is currently shifting from describing CD as an auto-immune condition to describing it as an immuno-deficiency.
Mycobacteria are the prime suspect for being the infection towards which the immune system responds inadequately in certain suceptible individuals.
Dr. Marcel Behr, professor in mycobacteria infections, present the research behind ts very well on this lecture:
Crohn's: autoimmune or infectious disease

As some of you may know, another research trajectory is currently preparing for a phase IIa study testing a purpose-built MAP-vaccine specifically made for Crohns's:
http://www.crohnsmapvaccine.com

So all in all exiting times, perhaps a glimmer of hope for finally getting treatments that address the root cause, and not just the symptoms of CD, in the years to come.
 
Location
San Diego
I suggest that Crohn's patients be very cautious and consult long and hard with their doctors before receiving any BCG vaccine. Because BCG is a LIVE vaccine, and as such poses a significant danger of Mycobacterium infection to anyone with suppressed or impaired immune system - such as Crohn's patients taking immunosuppressive therapy, especially biologics.

The warnings on my Stelara literature specifically and emphatically warn against BCG to anyone receiving Stelara therapy, warning of "serious and fatal" Mycobacterial infections.
 

my little penguin

Moderator
Staff member
Also understand Bch vaccine will give false positives on tb skin tests
In fact if you had Bcg as a child you can’t get a valid tb skin test and just use the blood test instead
 
I suggest that Crohn's patients be very cautious and consult long and hard with their doctors before receiving any BCG vaccine. Because BCG is a LIVE vaccine, and as such poses a significant danger of Mycobacterium infection to anyone with suppressed or impaired immune system - such as Crohn's patients taking immunosuppressive therapy, especially biologics.
The warnings on my Stelara literature specifically and emphatically warn against BCG to anyone receiving Stelara therapy, warning of "serious and fatal" Mycobacterial infections.
Highly relevant comment. There is a case report describing the tragic death of an infant, born by a mother with CD who was on Remicade during the pregnancy. Three month old the infant got the BCG vaccine, and soon thereafter died from TB.

Case Report: Fatal case of disseminated BCG infection in an infant born to a mother taking infliximab for Crohn's Disease

The MAP Vaccine development team is about to start vaccinating Crohn's patients. As I understand it the problem with subsequent TB infection it not an issue, though because they use a de-activated common cold-virus to deliver the DNA neede for the body to be able to start recognizing MAP as a pathogen and attack it.
I read about it in this transcript of a presentation about the MAP vaccine:
Dr. Amy Hermon-Taylor: The MAP Vaccine)

In the bottom of the transcript there is a Q n A session, and the questions give the impression that some central issues are either still not resolved, or the presenter is not aware of them:

Questions and answers from the presentation:

Audience: …How can you achieve a MAP viral titer with no adenoviral vector, and make sure that vaccine is working? Because one of the problems of vaccines is that you have to have the viral priming. Otherwise, you lose the ability to target specific cells. How do you do it with no adenoviral vector?

Dr. Hermon-Taylor: In all honesty, I don’t know the answer to that question, but the guys at the Jenner Institute are kind of the top experts in the world on that sort of thing. So I think they’re on the case.

Audience: OK.

Audience: I may have gotten it wrong, but isn’t one of the hypotheses that MAP actually triggers an autoimmune disease that is by its presence. And isn’t there some risk that if you introduce MAP in this way that it could make it worse?

Dr. Hermon-Taylor: It’s not the whole of MAP that you’re introducing with the vaccine. So, it’s just tiny pieces of DNA that you’ve taken out. It’s not the whole organism. It doesn’t

Audience 1: It stimulates an immune response, right?

Audience 2: Yes, but…it does it in a …system, so it doesn’t really affect the immune system. They’re building pieces, small pieces,

Audience 1: But it’s designed to stimulate an immune response.

Audience 2: But it’s not the same thing…
 
Thank you for posting this information.
It would be interesting to know the mechanism by which this microbiological vaccine can be used in a non infection environment.
Where is the logic behind this approach and what is it that activated the researcher to go beyond the microbial application.
Crohn and a few other GIs in the 1920s, 1930s tried vaccinating people with anti-dysentery serum (dysenteric poly-valent vaccine) and found excellent results, even in patients they knew had never had dysentery. They found that patients who had the best responses were those who suffered from a low level systemic septic shock from the vaccine - they further tested whether it was specifically the dysentery vaccine working on the disease itself or a general mechanism invoking a systemic response, by treating people with other things that also induced a septic shock (horse serum, mercury even) and found similar results, but only when such a shock occurred.

Effectively, the Qu biologic trial is a similar in some ways, but they are using a killed microbe (not serum from patients), specific to the gut ( e coli), but I suspect the mechanism is the same. The only difference is dose (I worked out that one doctor who put a patient in remission (who had UC), was injecting almost 300 mL of this stuff every 2nd day!!!), Qu does subcut injections of micromolar concentrations of e coli antigen.

I posited in both cases it is causing a reset of the upper cytokine/chemokine network that governs pro/anti inflammation (that happens after septic shock - dense systemic immunosuppression is how septicaemia kills by systemic organ failure in some cases).

Personally I think we can broadly push Crohn's into a disease with two over-arching mechanisms (general) - one in which mutations in a gene cause the anti-inflammatory cytokines/chemokines (Il-10 etc), to go down, which releases inhibition of pro-inflammation (so when a trigger comes on, be it a bug, a drug, a food antigen, etc), we get the slow chronic inflammation + flare ups. And on the other hand, we have mutations/dysregulations in genes that generally favour and drive inflammation (be it Il-6 etc). It's quite interesting to note that under this idea, where crohn's is mechanistically two entities, one expects that direct inhibition of a master regulator of inflammation would only generally work in 50 % of patients (if the hypothesis were true) ; which is pretty much the standard response rate (at least in Australia) for the anti-TNF Humira.

One of the biggies of septic shock (or serum shock) is TGF-B. I suspect the Qu trial, the Crohn's dysentery experiments etc, and possibly this study, induces that low level sepsis that, over time, "resets" this network of cytokines/chemokines into a more wild-type state, but bringing TGF-B and it's associate immuno-suppresors up, and aids in driving down the pro-inflammatory sneaky buggers.

I could write and write and write, but I already did 6000 words and pumped it off to a very unknown journal. When the reviews and edits come back I'll post the link, the literature points very sternly towards this idea, once you step back a bit and try to look at the whole picture.
 
Crohn and a few other GIs in the 1920s, 1930s tried vaccinating people with anti-dysentery serum (dysenteric poly-valent vaccine) and found excellent results, even in patients they knew had never had dysentery. They found that patients who had the best responses were those who suffered from a low level systemic septic shock from the vaccine - they further tested whether it was specifically the dysentery vaccine working on the disease itself or a general mechanism invoking a systemic response, by treating people with other things that also induced a septic shock (horse serum, mercury even) and found similar results, but only when such a shock occurred.

Effectively, the Qu biologic trial is a similar in some ways, but they are using a killed microbe (not serum from patients), specific to the gut ( e coli), but I suspect the mechanism is the same. The only difference is dose (I worked out that one doctor who put a patient in remission (who had UC), was injecting almost 300 mL of this stuff every 2nd day!!!), Qu does subcut injections of micromolar concentrations of e coli antigen.

I posited in both cases it is causing a reset of the upper cytokine/chemokine network that governs pro/anti inflammation (that happens after septic shock - dense systemic immunosuppression is how septicaemia kills by systemic organ failure in some cases).

Personally I think we can broadly push Crohn's into a disease with two over-arching mechanisms (general) - one in which mutations in a gene cause the anti-inflammatory cytokines/chemokines (Il-10 etc), to go down, which releases inhibition of pro-inflammation (so when a trigger comes on, be it a bug, a drug, a food antigen, etc), we get the slow chronic inflammation + flare ups. And on the other hand, we have mutations/dysregulations in genes that generally favour and drive inflammation (be it Il-6 etc). It's quite interesting to note that under this idea, where crohn's is mechanistically two entities, one expects that direct inhibition of a master regulator of inflammation would only generally work in 50 % of patients (if the hypothesis were true) ; which is pretty much the standard response rate (at least in Australia) for the anti-TNF Humira.

One of the biggies of septic shock (or serum shock) is TGF-B. I suspect the Qu trial, the Crohn's dysentery experiments etc, and possibly this study, induces that low level sepsis that, over time, "resets" this network of cytokines/chemokines into a more wild-type state, but bringing TGF-B and it's associate immuno-suppresors up, and aids in driving down the pro-inflammatory sneaky buggers.

I could write and write and write, but I already did 6000 words and pumped it off to a very unknown journal. When the reviews and edits come back I'll post the link, the literature points very sternly towards this idea, once you step back a bit and try to look at the whole picture.
Thanks for the information, and hope your paper makes the light of day!
 
SauceySciencey - thank you for sharing your research.
In your assessment the gene-mutation comes before the trigger, and you list a number of possible trigger mechanisms [... be it a bug, a drug, a food antigen...]

I would like to ask why you think the "classical" cascade of chronic infection, such as it is found with H.pylori and mycobacteria (MAP in this case) infection is not sufficient to explain the CD disease cascade? That is: the host is succeptible to (MAP) infection, host gets infected, disease occurs.
 
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my little penguin

Moderator
Staff member
Olej
It isn’t sufficient because it doesn’t explain everyone
Infants and children for example
Many have Crohns from birth on but do not have map infections ever
Honestly I think Crohns is like many things
If you look at juvenile idiopathic Arthritis (jia)
There used to be just a term known as juvenile rheumatoid arthritis (jra)
They don’t use that anymore
Jra was the disease but it really didn’t explain everyone
So now they have jia
Woth a lot of sub types and are still adding more to the classifications

Until they can classify the groups properly
Things get very muddy in the waters

The right classification allows you to determine which groups have which symptoms and do best with the right meds
Woth crohns it’s still the big umbrella term
Covering a wide variety of symptoms
They have a lot of work to do
 
my_little_penguin says:
It isn’t sufficient because it doesn’t explain everyone. Infants and children for example. Many have Crohns from birth on but do not have map infections ever

- Are you certain infants who develop CD symptoms had it from birth? Could it not be an infection contracted from breast eg. milk or formula? Also, would it not be very hard to diagnose a baby with CD right after birth, I mean, doing a scope and biopsy on a newborn does not sound like something one would want to do.
Also, data from a 2008 study suggests that CD in infants is extremely rare, like in 1% of pediatric CD:

Quote from study: The development of IBD in infancy is extremely rare. Published data from epidemiological studies and IBD registries in North America and Europe suggest that less than 1% of children with IBD present during the first twelve months of life.

my_little_penguin says:
With crohns it’s still the big umbrella term, covering a wide variety of symptoms

That is also what I read - and the reason I asked SauceySciencey about the cascade is that I am searching for evidence that at least a subset of CD patients express some sort of autoimmunity (antigens towards the body's own cells), but I have not found any.

For instance, this recent study from 2016 concludes:
In this review, antibody markers, including microbial antibodies, autoantibodies and peptide antibodies, will be described, focusing on their common features. At present, no single marker with qualities that are satisfactory for the diagnosis and treatment of IBD has been identified, although panels of some antibodies are being evaluated with keen interest.
 

my little penguin

Moderator
Staff member
We have parents here a small handful whose kids have had it since birth
Even if it’s 1%
When it’s your child that number doesn’t really matter
Ds was dx at age 7 which is only 2% risk
But was sick since birth
If it was infection multiple children from the same household exposed to the same infectious agents would have the disease given an infants immune system
Which does not happen

Ds was tested extensively for map with pcr etc... not present
So while map explains some in adults
It doesn’t explain kids since as you say Crohns is rare in infants and children
If it was in formula it would be wide spread

Kids it’s much more genetic and mutations since the phenotypes found are very different even by age of dx
 
SauceySciencey - from what I can understand, in very simple language, you believe that Qu or BCG etc., sort of resets the system that has gone awry? These treatments do not aim for a specific bug, but they sort of jump start the immune system to do its job...generally speaking? If this is correct, what causes the system to falter after 10, 15 or longer years doing just fine? Do you think a bacteria is involved? The idea that one is infected with MAP, which is slow growing so consequently not creating symptoms until later in life makes sense to me. Cattle are infected as calves but don’t show signs until much later in life. I feel like there needs to be a trigger. Infection, genetic mutations which prevent clearance of bug and then an event, perhaps a sickness, or massive stress... all of these colluding to bring on the disease.
 
SauceySciencey - from what I can understand, in very simple language, you believe that Qu or BCG etc., sort of resets the system that has gone awry? These treatments do not aim for a specific bug, but they sort of jump start the immune system to do its job...generally speaking? If this is correct, what causes the system to falter after 10, 15 or longer years doing just fine? Do you think a bacteria is involved? The idea that one is infected with MAP, which is slow growing so consequently not creating symptoms until later in life makes sense to me. Cattle are infected as calves but don’t show signs until much later in life. I feel like there needs to be a trigger. Infection, genetic mutations which prevent clearance of bug and then an event, perhaps a sickness, or massive stress... all of these colluding to bring on the disease.
The fact that many CD patients do not get sick before reaching their 50's or 60's is something I have heard GI's use as an argument against CD being (exclusively) autoimmune, but rather inability to respond to properly to an infection.
 
We have parents here a small handful whose kids have had it since birth
Even if it’s 1%
When it’s your child that number doesn’t really matter
Ds was dx at age 7 which is only 2% risk
But was sick since birth
If it was infection multiple children from the same household exposed to the same infectious agents would have the disease given an infants immune system
Which does not happen

Ds was tested extensively for map with pcr etc... not present
So while map explains some in adults
It doesn’t explain kids since as you say Crohns is rare in infants and children
If it was in formula it would be wide spread

Kids it’s much more genetic and mutations since the phenotypes found are very different even by age of dx
The PCR tests you had for mycobacterium infection may not give a definite answer. Culture has shown a better accuracy. (but does not nessecarily tell the specific kind of mycobacterium present).
The specialists' hypothesis is that there is a genetic predisposition that allows a trigger (infection) to result in chronic inflammation. So the trigger is not nessecarily MAP, I guess, but could be other agents. It would be very interesting to learn how many percent of IBD cases is caused by MAP. I hope future research will give that answer.

The theory explains why some children in a family gets it, others don't.
I am one of four kids, me and my sister has IBD, the two others has not. The logical explanation is we were probably all exposed to the trigger (mycobacterium, e.coli or others), but only my sister and I had the gene mutation allowing the development of IBD.
I tested positive for mycobacterium infection twice by culture. My sister has not been tested.
It is difficult to decide whether or not to keep childen off cows meat and dairy. My kid is allowed both, although I try to offer substitutes whenever feasible (plant based butter, oat or almond milk, soy yoghurt). Knock on wood - no symptoms, but I often think about whether I should stop buying milk for him all together. After all, there is a big chance he inherited the gene mutation from me.
 
OleJ - if I had it to do over again, I would have never given my kids milk. Ice cream perhaps on special occasions, but otherwise on a daily basis no. Regarding meat, if you cook it long enough, it should kill any MAP, but I don’t think the risk is as high as in dairy.
 
Mommabear - that makes sense. Also, the point about cooked meat is a good one. I thought about whether dead cells could invoke an immune response, but in a young child in which the disease has not been triggered (and hopefully never will be), this would not be an issue I guess.
 
OleJ - I’m no expert, but I don’t think dead cells would do that. It is the live ones that manage to get inside the immune cells and prevent them from doing their job, that cause all the problems. They are stealthy buggers!
 
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