Cavernous Malformation Thin walled, single layer of endothelium, cluster of bubble-like structures filled with stagnant blood Congenital or de novo Single or multiple Sporadic CCM 80% Familial CCM 20%
NM has highest density of inherited CM worldwide Autosomal dominant disorder Common Hispanic founder mutation Hundreds of families Large families Multiple lesions All ages Geographic and cultural isolation Limited availability of neurological and neurosurgical care in NM
Yr1Yr2Yr3Yr4Yr5 Aim 1: Database and clinical factors XXXXX Aim 2: GWAS and fine mapping XXXX Aim 3: Change in lesion burden XX Aim 1 Establish University of New Mexico 500 CCM1-CHM patients In collaboration with Angioma Alliance Aim 2 Modifier genes: clinical variability Lesion burden: primary outcome Potential surrogate for adverse outcomes Aim 3 longitudinal component natural history data with detailed imaging
The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. The cerebral cavernous malformation signaling pathway promotes vascular integrity via Rho GTPases. Nat Med Feb;15(2): Epub 2009 Jan 18 CCM2 mouse model, no CCM’s but increased permeability of skin Decreased permeability of skin with simvastatin
Saeid Taheri, PhD Blaine L. Hart, M.D. Anatomy and transfer rate in CCM: left to right, FLAIR image showing 3 CCMs; Ki (transfer rate) map; and VP (intravascular volume) map. 1)Use dynamic contrast-enhanced MRI (DCEMRI) to detect abnormalities in brain permeability in CCM patients and correlate with anatomic lesion information. 2)Compare change in permeability from baseline to three months in a group of CCM patients placed on statin medication with change in permeability for a control group of CCM patients not on statin medication, which could lay the basis for drug treatment trials for the larger CCM community. 3) Develop plans for a large blinded prospective clinical statin trial comparing outcome (number of hemorrhages, worsening of epilepsy) using permeability as a biomarker.