Cerebral Cavernous Malformations (CCM)

Cerebral cavernous malformation (CCM) is a serious genetic disease and approximately 200,000 Americans have had an incidence of bleeding in the brain from this disorder. In CCM disease endothelial cells form single or multiple cystic brain lesions that leak and may cause seizure, hemorrhagic stroke and neurological deficits. Inherited cases of CCM are caused by loss of function in one of the 3 CCM genes (CCM1, CCM2 and CCM3) and the numbers of lesions increase with age, increasing risk of a hemorrhagic event. Sporadic cases result from mutations in the same genes.

BA-1049 is the only new chemical entity in development to target the cause of the disorder. Studies of the inherited mutations underlying CCM formation revealed that disruption in endothelial barrier integrity is caused directly by the hyper-activation of ROCK. BA-1049 is a ROCK2 inhibitor, and targets the protein kinase that causes the disease.

Success with BA-1049 will be a transformative treatment. Currently, there are drugs that prevent or reverse CCM lesion formation. The only treatment of the underlying cause of symptoms is brain surgery to remove the CCM, potentially causing additional neurotrauma.


Other Neurovascular Disorders

The blood brain barrier is defective in many neurodegenerative diseases. Success with BA-1049 for treatment of CCM will have relevance to other neurological diseases that include stroke, ALS, and Alzheimer’s Disease.