Rapamycin for regulation of tight junction proteins

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?


It seems there is some ongoing research in this area. I’ve seen the data on Lupus and it seems intriguing


And clinical trials starting soon:


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: