Abstract Details

Title Subcutaneous Anti-CD20 Antibody Treatment Delays Gray Matter Atrophy in Human Myelin Oligodendrocyte Glycoprotein-Induced Experimental Autoimmune Encephalomyelitis Mice

Topic Multiple Sclerosis

Presentation(s) P14 - Poster Session 14 (8:00 AM-9:00 AM)

Poster/Presentation
Number 9-001

Objective To investigate the effect of subcutaneous mouse anti-CD20 antibody treatment on brain tissue-specific volumetric changes in the human myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis model (huMOG-EAE) of MS and to determine its effect on disease severity outcomes.

Background The huMOG-EAE model generates B-cell driven demyelination in mice, making it a suitable MS model to study B-cell depletion by anti-CD20 antibody treatment. We previously established that subcutaneous anti-CD20 antibody reduced the disability score in EAE induced by 200 µg huMOG_1-125 peptide, compared with isotype control, making it a robust model for studying neuroimaging effects of this therapy.

Design/Methods

8-week old C57Bl/6 mice (Jackson Laboratory, Bar Harbor, ME) were immunized with 200 µg huMOG_1-125 and treated with 50 µg/mouse of anti-CD20 (n=16) or isotype control (n=16) subcutaneously, starting 3 weeks pre-immunization and then weekly up to 3 weeks post-immunization. At Weeks 1 and 5 post-immunization, mice were examined with brain volumetric MRI scans (using 9.4T serial MRI). Disease severity was measured by clinical disability score (CDS) and performance on rotarod (test used to evaluate motor coordination and balance).

Results Subcutaneous anti-CD20 antibody treatment significantly reduced brain volume loss compared with the isotype controls across all timepoints longitudinally in the basal ganglia (p=0.01), isocortex (p=0.025) and thalamus (p=0.023). The CDS was reduced significantly with anti-CD20 antibody versus the isotype controls at Weeks 3 (p=0.003) and 4 (p=0.03), while a trend was observed at Weeks 5 (p=0.057) and 6 (p=0.086) post-immunization. Performance on rotarod was improved significantly at Weeks 3 (p=0.007) and 5 (p=0.01) post-immunization compared with the isotype controls.

Conclusions Subcutaneous treatment with anti-CD20 antibody delayed brain tissue neurodegeneration, especially in the gray matter, as measured in the basal ganglia, isocortex and thalamus, and showed clinical benefit on measures of disease severity in huMOG-EAE mice.

Authors/Disclosures
Suyog U. Pol, PhD (University At Buffalo - CTRC) PRESENTER	Dr. Pol has nothing to disclose.
	No disclosure on file
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.
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
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.
Gisbert Weckbecker	No disclosure on file
Robert Zivadinov, MD, PhD, F�鶹��ýӳ�� (Buffalo Neuroimaging Analysis Center)	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.

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