Treatment with Anti-mouse CD52 Antibody Is Associated with Preservation of Myelin and Maintenance of Axonal Conduction in the MOG-induced EAE Mouse Model (P1.220)

Objective: To assess the impact of treatment with anti-muCD52 antibody on preservation of myelin and axonal conductance in an experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis (MS). Background: MS is an autoimmune neurodegenerative disease characterized by demyelination in the brain and spinal cord, leading to decreased efficiency in axonal conductance and resulting in a broad spectrum of symptoms including impairment of motor function and neurological deficits. Clinical trials of alemtuzumab (anti-human CD52) in active relapsing-remitting MS patients have shown long-term benefit on sustained reduction of disability. The anti-muCD52 antibody was employed to explore the impact of anti-CD52 therapy on the level of myelination and axonal conductance in an EAE mouse model. Methods: Mice were immunized with myelin oligodendrocyte glycoprotein (MOG) peptide to induce EAE and treated with a 5-day course of anti-muCD52 antibody. The degree of myelination was assessed histologically and axonal conductance in the spinal cord was evaluated using spinal motor-evoked potentials (SMEP) as an index of spinal cord damage. Results: Treatment of mice with anti-muCD52 antibody resulted in significant depletion of circulating lymphocytes and reduction in disease scores compared to the control group. Histological analysis showed significant preservation of myelin in treated mice. In addition, a significant degree of axonal conductance was maintained (62% of normal) compared to the control group (26% of normal). SMEP measurements revealed improvement in both peak-to-peak amplitude and peak latency compared to the control group. This difference was observed as early as 3 days post-treatment and maintained throughout the course of the study. Conclusions: Histological and electrophysiological assessments in EAE mice provide direct evidence of a therapeutic benefit of anti-muCD52 treatment on myelin preservation and function of spinal cord motor neurons, which may contribute to the clinical benefit observed with alemtuzumab in MS patients. Study Supported by: Genzyme, a Sanofi company Disclosure: Dr. Huang has received personal compensation for activities with Genzyme Corp. Dr. Panghas received personal compensation for activities with Genzyme Corp. as an employee. Dr. Pande has received personal compensation from Genzyme Corp. as an employee. Dr. Turner has received personal compensation for activities with Genzyme Corp. as an employee. Dr. LaMorte has received personal compensation for activities with Genzyme Corp. Dr. Chretien has received personal compensation for activities with Sanofi-Aventis Pharmaceuticals, Inc. Dr. Garron has received personal compensation for activities with Genzyme Corp. as an employee. Dr. Roberts has received personal compensation for activities with Genzyme Corp. as an employee. Dr. Kaplan has received personal compensation for activities with Genzyme Corp. as an employee. Dr. Siders has received personal compensation for activities with Genzyme, Corp. as an employee.