New Drug Target Found to Halt Brain Vessel Defects

Researchers identify TIE2 receptor as key link between signaling pathways driving cerebral cavernous malformations.

Mar. 28, 2026 at 1:06am

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Researchers at the University of Pennsylvania's Perelman School of Medicine have discovered that the cell surface receptor protein TIE2 is the missing link between two signaling pathways that drive the growth of cerebral cavernous malformations (CCMs), abnormal blood vessel formations in the brain that can cause hemorrhages, strokes, and seizures. The study suggests drugs targeting TIE2 could prevent CCM formation.

Why it matters

CCMs are a common vascular condition that can have severe neurological consequences, but current treatment options are limited. Identifying TIE2 as a key regulator of the signaling pathways behind CCM growth provides a promising new drug target to chronically suppress this disease with potentially fewer side effects than existing treatments.

The details

The researchers found that TIE2 activity is enhanced in the endothelial cells surrounding CCMs, and that elevated MEKK3-KLF2/4 signaling increases TIE2 protein levels, leading to greater activation of the PI3K pathway. Inhibiting TIE2 with a drug called rebastinib prevented new CCM development in mice, suggesting TIE2 blockade could offer a more targeted approach than systemic PI3K pathway inhibitors.

  • The study was published on March 27, 2026 in the Journal of Experimental Medicine.

The players

Mark L. Kahn

A professor at the University of Pennsylvania's Perelman School of Medicine and the senior author of the study.

University of Pennsylvania

The institution where the research was conducted at the Perelman School of Medicine.

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What they’re saying

“Determining how endothelial cells augment PI3K signaling downstream of the MEKK3-KLF2/4 pathway could identify a more blood vessel–specific therapeutic strategy for chronic suppression of CCM growth.”

— Mark L. Kahn, Professor

What’s next

The researchers plan to further investigate the use of TIE2-inhibiting drugs like rebastinib as a potential treatment for CCMs.

The takeaway

This study's identification of TIE2 as a key link between signaling pathways driving CCM growth opens up a new, more targeted therapeutic approach to chronically suppress this dangerous vascular condition with potentially fewer side effects than existing options.