Antibody – VX15 Multiple Sclerosis
Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system characterized by immune cell infiltration, localized myelin destruction, and nerve cell death (1;2). Given the debilitating nature of the motor and sensory dysfunction associated with MS, there exists a significant need to identify novel therapeutic targets and strategies that safely and effectively slow progression and even reverse this disease. Specifically, a therapeutic that can promote remyelination and repair of damaged nerves, and protect against breakdown of the blood-brain barrier while simultaneously reducing inflammation, would represent a powerful and comprehensive approach toward mitigating disease severity.
VX15/2503 (anti-SEMA4D) has been shown in preclinical studies to promote remyelination and repair of damage to the Central Nervous System.
Myelin coating around axons in the brain and spinal cord is critical for neurological function. In MS, myelin is stripped from axons which may then degenerate. Healthy, mature oligodendrocytes are capable of remyelinating impaired axons. Preclinical data demonstrate that VX15/2503 promotes oligodendrocyte health by preventing cell death and inducing the differentiation of new mature myelin-producing oligodendrocytes. These are important steps in the process of remyelination and repair.
Blocking SEMA4D with VX15/2503 (anti-SEMA4D) has been shown in preclinical studies to be important for protecting the integrity of the blood brain barrier during neuroinflammatory disease.
The primary function of the blood-brain barrier (BBB) in people is to prevent entry of immune cells and toxic molecules into the brain and spinal cord. In MS, the BBB becomes permeable and allows for entry of immune cells including T cells which give rise to lesions. Preclinical studies suggest that SEMA4D interacts with the endothelial cells that constitute the BBB to create gaps in the barrier that allow immune cells and molecules to cross into the brain. It was also demonstrated in these studies that blocking SEMA4D with VX15/2503 protects the integrity of the BBB.
VX15/2503 (anti-SEMA4D) has been shown in preclinical studies to reduce inflammation.
SEMA4D is expressed at high levels on B and T cells, two cell types that play an important role in inflammatory diseases like MS and rheumatoid arthritis (RA). In animal models of RA, VX15/2503 has been shown to significantly reduce disease severity by reducing inflammatory damage to joints and bone tissue. MS is also believed to be an immune-mediated disorder and autoimmune T cells, in particular, have been implicated in destruction of normal neuronal tissue. In several different animal models of MS, we have shown that VX15/2503 is capable of blocking SEMA4D-induced activation of inflammatory cells and reducing the number of immune cells that accumulate abnormally in the brain and spinal cord during disease.
VX15/2503 - Vaccinex is currently conducting a Phase I clinical trial of VX15/2503 monoclonal antibody in adult patients with Multiple Sclerosis. This is a single, ascending dose trial measuring safety and tolerability. For further information and eligibility criteria, please refer to the National Institutes of Health ClinicalTrials.gov Web site listed below.
Adams,C.W. 1977. Pathology of multiple sclerosis: progression of the lesion. Br. Med. Bull. 33:15-20.
Prineas,J. 1975. Pathology of the early lesion in multiple sclerosis. Hum. Pathol. 6:531-554.