MIT Researchers Link Rett Syndrome to Leaky Brain Vessels

Study finds two common genetic mutations in Rett syndrome compromise blood vessel integrity through overexpression of a microRNA.

Published on Feb. 26, 2026

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MIT researchers have discovered that two common genetic mutations that cause Rett syndrome each set off a molecular chain of events that compromises the structural integrity of developing brain blood vessels, making them leaky. The study traces the problem to overexpression of a particular microRNA (miRNA-126-3p), and shows that tamping down the miRNA's levels helps to rescue the vascular defect.

Why it matters

Rett syndrome is a severe developmental disorder affecting both the brain and body, and the researchers' findings suggest that vascular problems are a central feature of the disease. Understanding the molecular mechanisms behind the leaky brain vessels could lead to new treatment approaches targeting the microRNA implicated in the study.

The details

The researchers developed advanced human tissue cultures to model vessel development, with and without the MeCP2 mutations that cause Rett syndrome. They found that the vessels harboring either mutation showed reduced expression of a protein called ZO-1, which is critical for ensuring tight seals between endothelial cells. Further tests showed the Rett-mutation vessel cultures were relatively leaky compared to controls. The team also found that miRNA-126-3p was overexpressed in the Rett cultures, and treating the cultures with a molecule that reduces miRNA-126-3p levels resulted in an increase in ZO-1 expression and a partial restoration of endothelial cell barrier function.

  • The study was published in Molecular Psychiatry in 2026.

The players

Tatsuya Osaki

Lead author and research scientist who developed the advanced human tissue cultures used in the study.

Mriganka Sur

Senior author, Newton Professor of Neuroscience at MIT's Picower Institute and Department of Brain and Cognitive Sciences.

Roger D. Kamm

Co-author, Professor of Mechanical Engineering and Biological Engineering at MIT.

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What they’re saying

“A role for microRNAs in Rett syndrome has been shown, but now demonstrating that miRNA-126-3p is actually downstream of MeCP2 and directly implicated in the endothelial cell dysfunction is an important piece of the Rett syndrome puzzle.”

— Mriganka Sur, Newton Professor of Neuroscience (Molecular Psychiatry)

“That's why we hypothesized that we should have some mediator between the MeCP2 mutation and ZO-1 downregulation and the BBB permeability increase. We focused on the microRNAs.”

— Tatsuya Osaki, Lead Author and Research Scientist (Molecular Psychiatry)

What’s next

The researchers are planning to administer a drug called miRisten, which inhibits miR-126, to mice modeling Rett syndrome to see if it helps improve the vascular defects.

The takeaway

The study's findings suggest that vascular problems are a central feature of Rett syndrome, and that targeting the overexpression of miRNA-126-3p could be a promising therapeutic approach for addressing the leaky brain vessels associated with the disease.