Anti-murine CD52 therapy provides anti-inflammatory and neuroprotective effects in an EAE mouse model (THER3P.888)

To better understand the mechanism of action of alemtuzumab in multiple sclerosis (MS), we have investigated the effects of anti-mouse CD52 antibody (anti-muCD52) treatment in an EAE mouse model. Therapeutic administration of anti-muCD52 antibody significantly reduced the severity and progression of disease. Treatment benefit was associated with a reduction in the number of lymphocytes in the spleen and CNS as well as a reduction in MOG35-55 auto-reactive T cells that produce IFNγ or IL-17 following ex vivo restimulation. Neuroprotective effects were also observed following antibody treatment. Specifically, anti-muCD52 treatment reduced the level of white matter damage in the CNS as determined by histological analysis of myelin basic protein and by measurement of serum phosphorylated neurofilament heavy chain. In addition, axonal conductance of the spinal cord was assessed through electrophysiological measurement of motor-evoked potentials. Animals treated with anti-muCD52 demonstrated higher peak amplitude as well as reduced peak latency compared to control animals treated with vehicle. Collectively, these results suggest that the therapeutic benefit of anti-muCD52 treatment in EAE can be attributed in part to a reduction in the number of auto-reactive T cells, decreased CNS inflammation, and protection of CNS integrity.