Development of a Mouse Model of Sturge-Weber Syndrome and Therapeutic Response to Imatinib

Sturge-Weber Syndrome (SWS) is a common vascular malformation caused by mutation of GNAQ in endothelial cells. No effective medical therapy exists for SWS, and therapy is mainly surgical. Progress in the medical treatment of SWS has been hindered by the lack of an animal model. We introduced mutant GNAQ into an immortalized murine endothelial cell line, MS1. The resultant cells form slow growing vascular malformations that morphologically and biochemically resemble human SWS. One of the genes upregulated as a result of mutant GNAQ is c-kit, which is a targetable event. Given that the FDA approved drug imatinib targets c-kit as well as its original target, bcr-abl, we evaluated the ability of imatinib to prevent the growth of vascular malformations in mice. We saw that imatinib significantly inhibits the growth of vascular malformations in vivo. Repurposing of imatinib for the treatment of SWS should be evaluated in a clinical trial. ATAC-seq analysis.