ATORVASTATIN IN CEREBRAL CAVERNOUS MALFORMATION: ELUCIDATING ROCK INHIBITION AND LIPID-LOWERING MECHANISMS FOR THERAPEUTIC REPURPOSING

Abstract

Cerebral cavernous malformations (CCMs) are vascular abnormalities in the central nervous system that can lead to seizures, haemorrhagic stroke, and neurological deficits. Emerging evidence implicates the RhoA/ROCK signaling pathway in CCM pathogenesis, where its hyper activation disrupts endothelial junctions and promotes vascular leakage. Atorvastatin, a widely used lipid-lowering agent has demonstrated inhibitory effects on RhoA prenylation and downstream ROCK activity, offering endothelial-stabilizing and anti-inflammatory benefits. Preclinical models and early clinical trials suggest that atorvastatin reduces lesion burden and improves vascular integrity in CCMs. Given its favorable safety profile and dual mechanism of action, atorvastatin presents a promising candidate for therapeutic repurposing in CCM management.