Novel Therapy for Multiple Sclerosis Discovered

Semaphorin 4D (SEMA4D) is a viable target for therapy in neuroinflammatory and neurodegenerative diseases like multiple sclerosis (MS), according to findings published in Neurobiology of Disease.

Researchers from Vaccinex, Inc. in Rochester, New York conducted a study of mouse models of experimental autoimmune encephalomyelitis (EAE) — a surrogate for human MS – in order to determine if SEMA4D or any specific novel molecular therapy would make a viable target. The investigators created a monoclonal antibody which binds animal model SEMA4D with high affinity and inhibits the binding between SEMA4D and its receptors. In the process, anti SEMA4D binds in vitro to the recombinant SEMA4D, which prohibited the survival and differentiation of oligodendrocytes precursor cells (OPCs) – important for maintaining the myelin coating on neurons. The EAE rodents demonstrated anti SEMA4D significantly inhibited the development of the neurodegenerative diseases by preserving the BBB integrity and axonal myelination.

A further result the researchers noted was that anti SEMA4D tended to aid the migration of OPC to the site of lesions and improved myelin status after inducing demyelination chemically.

The researchers found that in 3 causes of neuroinflammatory disease, which included the breakdown of the brain blood barrier (BBB), apoptosis of OPCs, and activation of microglia, SEMA4D was effective in blocking the activity. Antibodies were vital to this blocking process, the researchers found.

Vaccinex is currently testing an antibody that blocks human SEMA4D called VX15/2503 in a phase 1 clinical trial. That study is designed to test the safety and tolerability in human patients with MS. The results of this study are expected to be available in early 2015. Vaccinex is a clinical stage biotechnology company which focuses on the discovery and development of human therapeutic monoclonal antibodies to treat cancer and neurodegenerative diseases such as MS and Huntington’s disease.