EnrQay
#1
In Dr. Green’s recent Baylor U presentation, he noted research that showed that rapa protected the integrity of the blood-brain barrier by downregulating MMP-9, which downregulates tight junction proteins. This may reduce Alzheimers disease.
I then searched for papers on MMP-9 in the gut, since one common but unproven theory is that when the gut is too permeable, various autoimmune diseases are initiated or exacerbated.
A 2015 study on colitis “suggest[s] a role of MMP-9 in modulation of colonic epithelial permeability and inflammation”
A 2021 study showed the mechanism MMP-9 regulation of tight junction gut permeability was through an activation of the NF-κB protein complex.
MMP-9 and other metalloproteinases are also dysregulated in type 1 diabetes, probably due to the higher blood glucose levels.
Other similar papers can be found on inflammatory bowel disease and ulcerative colitis.
The question is: will rapamycin’s downregulation of MMP-9 alter the course of some autoimmune diseases?
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It seems there is some ongoing research in this area. I’ve seen the data on Lupus and it seems intriguing
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(18)30485-9/fulltext
And clinical trials starting soon:
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EnrQay
#3
I found no studies, prospective or completed, pertaining to sirolimus, type 1 diabetes, and gut permeability. Most studies that use sirolimus on T1D are about islet transplant tolerance.
Two studies looked at sirolimus as a therapeutic:
This one was positive in terms of exogenous insulin required and average blood glucose:
Another that used a combination sirolimus / IL-2 therapy was partly positive and partly negative, particularly during the IL-2 phase of the trial. Tregs were increased but effector T-cells were unchanged:
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