While past clinical studies to treat stroke have focused on neuroprotection, the extent of the vascular defect that follows ischemic stroke is largely predictive of outcome. When the blood-brain-barrier is greatly compromised there is increased edema and risk of hemorrhagic transformation. BioAxone’s BA-1049 reverses the loss of endothelial cell barrier function that follows stroke. In preclinical models of reperfusion injury, BA-1049 reduces endothelial barrier dysfunction. Therefore, BA-1049 is promising drug candidate for treatment of acute stroke to reverse endothelial cell defects, and to increase adaptive plasticity of neurons.

Cerebral Cavernous Malformations (CCM)

Angioma (also called 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 angioma, endothelial cells form single or multiple cystic brain lesions that leak and may cause seizure, hemorrhagic stroke and neurological deficits. Inherited cases of angioma 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 angioma 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 no drugs that prevent or reverse angioma lesion formation. The only treatment of the underlying cause of symptoms is brain surgery to remove the angioma, 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.