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Mass. General study finds potential mechanism for BCG vaccine reversal of type 1 diabetes

Hip

Senior Member
Messages
17,824
Very interesting. It says in the BCG vaccine clinical trial for type 1 diabetes that:
2 BCG vaccinations spaced 4 weeks apart during the first year and then 1 vaccination every year for the next 4 years

The cost of a single BCG vaccination at a private clinic in the UK is around £80.

The mechanism of action seems to be based on the effect BCG vaccine has on regulatory T cells, as your article states:
BCG may induce a permanent increase in expression of genes that restore the beneficial regulatory T cells (Tregs) that prevent the immune system from attacking the body's own tissue.

Whether this would have any application in ME/CFS is uncertain: unlike in type 1 diabetes, where the immune system attacks and destroys the insulin-secreting beta cells of the pancreas, as far as well know in ME/CFS there are no cells in that are being attacked and destroyed.
 

Murph

:)
Messages
1,799
This is seriously amazing. They are only 3 years into a nine year process for their Phase II trial though. It'll be a while until they're ready to go to Phase III.

Still. very promising and I suspect the sort of treatment that might catch on for diabetes even before the data is in, since it's considered very safe.

Is it relevant for us? Not sure but definitely exciting to have whole new methods being developed. I've said before and I'll say again that given the amount of money and effort going to other diseases, the breakthroughs that help us are most likely to have their origins in seemingly unrelated disease areas. (e.g. fluge and mella or even really naviaux and his metablomics)
 

M Paine

Senior Member
Messages
341
Location
Auckland, New Zealand
I can't say that I've looked into this deeply (too much PEM at the moment). I have the same sort of questions about mechanism, and what evidence they have for the suggested TReg epigenetic changes they suggest in the original link.

One thing that caught my eye with this, was the strain of bacteria they are vaccinating against. Mycobacterium are quite interesting in general. The cousin of TB, MAP (Mycobacterium avium paratuberculosis) infection in the GI Tract is being looked at as a potential cause of Crohn's disease (an autoimmune disorder). Being both difficult to treat with antibiotics, and difficult to culture, and difficult to sequence, it's a bit of a nasty one.

Anyway, I found it curious @Murph that they need to do phase II and phase III trials, for some reason I thought this might be an already tested vaccine which was being re-purposed. I don't know why I got that impression.
 

Forbin

Senior Member
Messages
966
Is this a microbiome-related thing?

It kind of sounds like high levels of mycobacteria (in the gut?), promoted by "modern diet" and "hygiene," suppress the very Tregs that would normally moderate them, creating a self-sustaining imbalance that also leads to auto-immunity elsewhere (in the pancreas) due to the suppression of Tregs. From the wording of the article, I'm guessing that the BCG vaccine stimulates the Tregs to suppress the overgrowth of the mycobacteria, thus ending the imbalance that "weakened" the Tregs in the first place. The resurgent Tregs are then able prevent the autoimmunity that's causing type 1 diabetes.

It would be sort of like giving the underdogs in a battle a temporary "shot in the arm" so they could get on their feet and set things right again.

Or am I totally wrong about this?:confused:
 

M Paine

Senior Member
Messages
341
Location
Auckland, New Zealand
Straight off wikipedia - "In medicine, the hygiene hypothesis is a hypothesis that states a lack of early childhood exposure to infectious agents, symbiotic microorganisms (such as the gut flora or probiotics), and parasites increases susceptibility to allergic diseases by suppressing the natural development of the immune system."

It's not clear to me exactly what mechanism this group is suggesting... but my interpretation was that the absence of TReg activity might be associated with a decline in parasitic infection. In other words the vacinne is dampening the immune system by similar mechanisms which might occur if a person was exposed to these pathogens, which in some cases may be asymptomatic/benign to begin with.
 

Murph

:)
Messages
1,799
Anyway, I found it curious @Murph that they need to do phase II and phase III trials, for some reason I thought this might be an already tested vaccine which was being re-purposed. I don't know why I got that impression.

It is definitely an already tested vaccine, FDA approved for tuberculosis inoculation and other uses. It's proven safe but I guess they need to prove it is effective, and for such an unusual use case you want high quality data and the best possible process.
 

Murph

:)
Messages
1,799
Here's a very intriguing counterpoint. (albeit note that I can't be sure the open endocrinology journal isn't a rubbish bin of loonies)

Discontinuation of BCG Vaccination Precedes Significant Drop in Type 2 Diabetes in Japanese Children. Role of Inflammation and Cortisol Activity as a Cause of Type 2 Diabetes

BCG immunization was routinely given to elementary and junior high school students in Japan until it was abruptly discontinued after 2002. Data on the incidence of type 2 diabetes was analyzed to see if there was a change fol- lowing discontinuation of BCG. The incidence of type 2 diabetes dropped by over 50% in children from Tokyo following discontinuation of BCG immunization, the relative risk reached 2.78 (95% confidence interval 1.03 - 7.480). This drop appears to be more significant given the epidemic of type 2 diabetes in children around the world. The increased secretion of cortisol following immunization is thought to result in metabolic syndrome and type 2 diabetes. Japanese children pro- duce larger amounts of cortisol following immunization than White children. This increased production of cortisol may explain why Japanese children have a high risk of type 2 diabetes but low risk of type 1 diabetes compared to White chil- dren. The proposed mechanism may explain the epidemic of obesity which starts in children under 6 months of age.
Discontinuation of BCG Vaccination Precedes Significant Drop in Type 2 Diabetes in Japanese Children. Role of Inflammation and Cortisol Activity as a Cause of Type 2 Diabetes. Available from: https://www.researchgate.net/public...rtisol_Activity_as_a_Cause_of_Type_2_Diabetes [accessed Jun 12, 2017].

https://www.researchgate.net/public...rtisol_Activity_as_a_Cause_of_Type_2_Diabetes