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Abstract Details

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
Multiple Sclerosis
P2 - Poster Session 2 (8:00 AM-9:00 AM)
9-013
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. 

The effect of anti-CD52 treatment on slowing-down neurodegeneration and microglia activation in multiple sclerosis (MS) is unknown.

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.

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.
Anti-muCD52 treatment does not provide benefit in the TMEV model of demyelination on behavioral, MRI, histology and immunochemistry outcomes. 
Authors/Disclosures
Robert Zivadinov, MD, PhD, FÂé¶¹´«Ã½Ó³»­ (Buffalo Neuroimaging Analysis Center)
PRESENTER
The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for BMS. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Omnicuris. The institution of Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Myrobalan. Dr. Zivadinov has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi. Dr. Zivadinov has received personal compensation in the range of $10,000-$49,999 for serving on a Speakers Bureau for EMD Serono. Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bristol Myers Squibb. The institution of Dr. Zivadinov has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Biogen.
Ferdinand Schweser, PhD (SUNY University At Buffalo) Dr. Schweser has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Elsevier.
Michael G. Dwyer III, MD, PhD (Buffalo Neurological Analysis Center) Dr. Dwyer has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Bristol Myers Squibb. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Keystone Heart, Ltd. Dr. Dwyer has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Novartis. The institution of Dr. Dwyer has received research support from Novartis. The institution of Dr. Dwyer has received research support from Keystone Heart, Ltd. The institution of Dr. Dwyer has received research support from Bristol Myers Squibb. The institution of Dr. Dwyer has received research support from Roche.
Suyog U. Pol, PhD (University At Buffalo - CTRC) Dr. Pol has nothing to disclose.