Effect of Anti-muCD52 antibody on Brain and Spinal Cord Imaging Markers of Neurodegeneration, Microglia, and Macrophage Activation in the Theiler’s Murine Encephalomyelitis Virus Model of Chronic Demyelination (2486)

Objective: To investigate the effect of anti-muCD52 treatment on changes of brain and spinal cord imaging, histology and immunochemistry markers in the Theiler’s Murine Encephalomyelitis Virus (TMEV) mouse model of chronic demyelination. Background: The effect of anti-CD52 treatment on slowing-down neurodegeneration and microglia activation in multiple sclerosis (MS) is unknown. Design/Methods: Mice were infected with TMEV at 7 weeks of age and treatment with anti-muCD52 or vehicle placebo (VHPLC) was started at 3 months post-infection (pi). 36 mice were treated with anti-muCD52 and 36 with VHPLC. There were 3 groups of 24 mice treated with either anti-muCD52 (n=12) or VHPLC (n=12) that underwent different imaging protocols. Group 1 was scanned with brain imaging that evaluated regional volumes, quantitative susceptibility mapping, magnetic resonance spectroscopy metabolites and leptomeningeal enhancement, group 2 with spinal cord imaging that assessed number and volume of T2 lesions, while group 3 examined the detection of ultra-small particle iron oxide positive enhancing lesion number and volume in the brain, as biomarkers of microglia and macrophage activity. MRI, behavioral testing and blood collection for serum analysis was performed for Groups 1 and 2 at months 3, 5, 7 and 9 month pi, and for Group 3 at 4, 5 and 7 month pi, in addition to pre-treatment baseline assessments (month 3 pi). Histology, immunochemistry markers and viral TMEV transcript, were also assessed. Results: In total 12 antimu-CD52 and 6 VHPLC treated animals died during treatment phase (p=0.136) phase of the study. The clinical score disease severity was significantly higher in anti-muCD52, compared to the VHPLC treated animals (p=0.03). No significant differences in brain and spinal cord MRI endpoints, and histology or immunochemistry markers were found between the treatment arms. Conclusions: Anti-muCD52 treatment does not provide benefit in the TMEV model of demyelination on behavioral, MRI, histology and immunochemistry outcomes. Disclosure: Dr. Zivadinov has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Received personal compensation from EMD Serono, Genzyme-Sanofi, Celgene, and Novartis. Dr. Zivadinov has received research support from Received financial support for research activities from Genzyme-Sanofi, Novartis, Celgene, KeyStone Heart, V-WAVE Medical, Mapi Pharma and Protembis.Dr. Schweser has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Ferdinand Schweser received personal compensation from Toshiba Canada Medical Systems Limited, Canon Medical Systems Corporation Japan, and Goodwin Procter LLP for speaking and consultant fees.. Dr. Schweser has received research support from Ferdinand Schweser received financial support for research activities from SynchroPET Inc. and travel sponsorship from GE Healthcare and SynchroPET Inc.. Dr. Dwyer has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with Serono Novartis and Clare Medical.. Dr. Dwyer has received research support from Michael G. Dwyer received financial support for research activities from Mapi Pharma, Keystone Heart, Protembis and V-WAVE Medical.. Dr. Pol has nothing to disclose.