Treatment options emerging for CCMs

BOSTON—BioAxone BioSciences, Inc., a biotechnology company committed to applying an innovative understanding of axon regeneration and neuronal signaling to transform the lives of patients afflicted with neurotrauma or neurovascular disorders, has announced the publication of an article in Translational Stroke Research.

The published data indicated that BA-1049 has promise as a therapeutic agent for the treatment of cavernous angioma (CA). CA is a rare genetic disease with no current treatment available, other than surgical removal of the brain lesions. BA-1049 is a first-in-class oral inhibitor of Rho Kinase 2 (ROCK2) that has shown a promising safety profile and efficacy in multiple preclinical models of neurovascular disease.

“The data from the study support BA-1049 as a potentially transformative therapy to repair the thin-walled, leaky capillaries that predispose CA patients to a lifetime risk of seizure, hemorrhagic stroke and other neurological defects,” said Lisa McKerracher, Ph.D., CEO of BioAxone BioSciences. “We look forward to future studies to glean further understanding about the impact of BA-1049 as we work to treat angioma and potentially reverse progression of the disease.”

CA (also called cerebral cavernous malformation, aka CCM) is a serious genetic disease. 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). The numbers of lesions increase with age, increasing the risk of a hemorrhagic event. Sporadic cases of this disorder can result from mutations in the same genes.

CA can be clearly diagnosed by imaging, but there are currently no pharmacological treatment options. The standard of care is watchful waiting until neurosurgical removal is deemed un-avoidable. No drug treatments are currently available to address or prevent leakiness or hemorrhage. The progression of individual lesions is variable and unpredictable, leaving patients unable to prepare for or prevent reoccurrence of symptoms following their diagnosis.

The study, funded by an NIH Small Business Innovation Grant, was a collaboration between BioAxone, Dr. Doug Marchuk of Duke University and Dr. Issam Awad of University of Chicago. It was designed to investigate the role of ROCK2 in the development of CA and the functional impact of ROCK2 inhibition.

The study demonstrates that BA-1049 has a promise to reduce CA disease progression for mild and aggressive forms of the disease, both by reducing non-heme deposition near lesions and by reducing lesion growth and maturation. It also shows a promising safety profile after long-term (3–4 months) oral administration. BA-1049 treatment could provide alternatives to surgical removal of symptomatic CAs, and BioAxone intends to undertake further development of the BA-1049 for reducing the burden of CA disease.