Overview
- Researchers from Penn reported in the Journal of Experimental Medicine on Friday that blocking the endothelial receptor TIE2 prevented new cerebral cavernous malformation lesions in mice.
- TIE2 sits on the surface of blood vessel cells and links the MEKK3–KLF2/4 signal to PI3K activation, which drives the growth of these fragile brain vessel clusters.
- The team found higher TIE2 activity around human and mouse lesions and showed that the oral drug rebastinib, which targets multiple tyrosine kinases, shut down new lesion formation in animal models.
- CCMs can affect about 1 in 200 people, often form in spots where surgery is risky, and can lead to brain bleeds, seizures, or stroke, which leaves a major need for medical treatments.
- Prior mouse studies showed PI3K inhibitors can halt CCMs but carry broad toxicities, so targeting TIE2 may offer a more precise route, with human safety and efficacy now the key next tests.