Blocking Signalopathic Events to Treat Cerebral Cavernous Malformations

Cerebral cavernous malformations (CCMs) are caused by the clonal loss of any of three CCM genes within endothelial cells of lowly perfused venous capillary vessel beds. In mouse models of CCM, cavernoma growth is spurred when CCM-deficient clones of vessel-resident endothelial progenitor cells recruit wild-type neighboring endothelial cells. Increasing evidence suggests that nongenetic ‘third hits’ cause an activation of quiescent CCM-deficient...