Rapamycin for regulation of tight junction proteins

#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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Any experience with Rapamycin as an alternative to Prednisone for Polymyalgia Rheumatica (PMR)?
#2

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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#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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