MIT Researchers Uncover Role of MicroRNA in Rett Syndrome Brain Vessel Leakage

Study links common genetic mutations to compromised blood-brain barrier, offering new therapeutic insights

Apr. 11, 2026 at 11:20am

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A highly structured abstract painting in muted earth tones, featuring sweeping geometric arcs, concentric circles, and precise botanical spirals, conceptually representing the intricate molecular mechanisms behind Rett syndrome's impact on the brain's vascular system.An abstract scientific illustration depicting the complex molecular pathways disrupted in Rett syndrome, leading to compromised brain blood vessels and potentially impacting neurological function.Cambridge Today

Groundbreaking research from MIT's Picower Institute has revealed how two common genetic mutations associated with Rett syndrome lead to leaky brain blood vessels through the overexpression of a specific microRNA. The findings provide critical insights into the neurological impacts of Rett syndrome and point to potential new treatment approaches targeting this molecular pathway.

Why it matters

Rett syndrome is a severe developmental disorder that primarily affects young girls, causing a range of neurological and physical impairments. Understanding the underlying mechanisms driving the condition's vascular and neural dysfunction is crucial for developing more effective therapies. This study's focus on the role of microRNAs in disrupting the blood-brain barrier offers a promising new avenue for intervention.

The details

The MIT researchers, led by Tatsuya Osaki and senior author Mriganka Sur, developed advanced human tissue cultures to model the effects of two common MeCP2 gene mutations associated with Rett syndrome on vascular development. They found that both the R306C and R168X mutations led to the overexpression of microRNA-126-3p, which in turn reduced the expression of the critical protein ZO-1, compromising the integrity of the endothelial cell junctions and resulting in leaky blood vessels. Exposing neurons to the secretions from these Rett-mutation vessel cultures also disrupted the neurons' electrical activity, suggesting a potential mechanism for the neurological impacts of the disease.

  • The study was published in Molecular Psychiatry in April 2026.

The players

Tatsuya Osaki

Lead author of the study and a researcher at The Picower Institute for Learning and Memory at MIT.

Mriganka Sur

Senior author of the study and the Newton Professor of Neuroscience at MIT.

Rett Syndrome

A severe developmental disorder that primarily affects young girls, causing a range of neurological and physical impairments.

MeCP2 gene

The gene that, when mutated, is associated with Rett syndrome.

microRNA-126-3p

A specific microRNA that was found to be overexpressed in Rett syndrome vessel cultures, leading to compromised blood-brain barrier integrity.

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What they’re saying

“Demonstrating this connection between MeCP2 mutations, microRNA-126-3p overexpression, and vascular dysfunction is a significant step forward in understanding the Rett syndrome puzzle.”

— Mriganka Sur, Newton Professor of Neuroscience at MIT

What’s next

The researchers plan to administer a drug called miRisten, which inhibits miR-126, to mice modeling Rett syndrome to assess its potential therapeutic benefits.

The takeaway

This study's findings on the role of microRNAs in disrupting the blood-brain barrier in Rett syndrome open up new avenues for developing targeted interventions to address the neurological impacts of this debilitating disorder.