Cerebral Cavernous Malformations (CCM)
We are investigating the biology of Ccm3, one of three genes implicated in the pathogenesis of CCM, a monogenic cerebrovascular disorder. We have generated a mouse model that develops vascular lesions highly similar to human cavernomas; its study has led to the identification of cell autonomous as well as cell non-autonomous functions of CCM3 in vascular and neural development, and has unraveled an important role of this protein in the neurovascular unit. Using high-throughput screening we recently discovered that fluvastatin and zoledronate, two drugs already approved for clinical use for other indications, act synergistically to reverse outcomes of CCM3 loss in primary cells and animal models of CCM in vivo. Our studies suggest that combined therapy targeting the mevalonate pathway might have therapeutic effects in CCM disease.
- Combined HMG-COA reductase and prenylation inhibition in treatment of CCM.Nishimura S, Mishra-Gorur K, Park J, Surovtseva YV, Sebti SM, Levchenko A, Louvi A, Gunel M. Proc Natl Acad Sci U S A. 2017 May 23; 2017 May 12. PMID: 28500274.
- Ccm3, a gene associated with cerebral cavernous malformations, is required for neuronal migration.Louvi A, Nishimura S, Günel M. Development. 2014 Mar. PMID: 24595293.
- Loss of cerebral cavernous malformation 3 (Ccm3) in neuroglia leads to CCM and vascular pathology.Louvi A, Chen L, Two AM, Zhang H, Min W, Günel M. Proc Natl Acad Sci U S A. 2011 Mar 1; 2011 Feb 14. PMID: 21321212.