Abstract Details

Title Effect of LINGO-1 Blockade on Optic Nerve Axonal Injury in MOG-EAE Rodent Models

Topic MS and Related Diseases

Presentation(s) P05 - (-)

Poster/Presentation
Number 186

Objective

Background BACKGROUND: LINGO-1 inhibits CNS oligodendrocyte differentiation, myelination and axon regeneration. Inhibition of LINGO-1 with the monoclonal antibody BIIB033, an investigational treatment for multiple sclerosis (MS), promotes axonal integrity/remyelination in the spinal cord of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-EAE).

Design/Methods DESIGN/METHODS: Two studies were performed in MOG-EAE models. In the first study, after EAE induction in C57BL/6 mice, BIIB033 or negative control antibody (cAb) was administered by intraperitoneal (IP) injection (2 cohorts, n=7 each, BIIB033 or cAb). Assessments included clinical severity, diffusion magnetic resonance imaging (MRI) and histology. In the second study, after EAE induction and onset, Brown Norway rats were treated for 3 days with either methylprednisone (MP; dose/duration mimicking clinical treatment of AON) or vehicle (Veh). Beginning on Day 2 of MP treatment, animals were given 3 once-weekly IP doses of either BIIB033 or cAb. Axonal pathology was assessed 1 week after the final BIIB033 by microscopy and immunohistochemistry.

Results RESULTS: In mice, EAE severity was reduced with BIIB033 treatment relative to cAb. The apparent diffusion coefficient parallel to the long axis of the optic nerve (longitudinal diffusivity) was higher with BIIB033 than cAb (means, 1400 ms versus 1183 ms, respectively; P<0.01). Axonal atrophy in optic nerves was reduced by 13% with BIIB033 relative to cAb (P=0.07). In rats treated with Veh + cAb, there was marked axonal loss in optic nerves;axonal numbers were slightly higher in rats treated with MP + cAb. In contrast, axonal loss was reduced 5-fold in rats treated with Veh + BIIB033 (P<0.01) and 8-fold in rats treated with MP + BIIB033 (P<0.001).

Conclusions CONCLUSIONS: LINGO-1 inhibition with BIIB033 reduced optic nerve axonal injury/axonal loss in MOG-EAE rodent models, supporting further investigation of thepotential CNS neuroprotective role of BIIB033 in the clinic.

Authors/Disclosures
Diego Cadavid, MD, FAAN (Verge Genomics) PRESENTER	Dr. Cadavid has received personal compensation for serving as an employee of Verge Genomics. Dr. Cadavid has received personal compensation for serving as an employee of Vertex Pharmaceuticals. Dr. Cadavid has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novo Nordisk. Dr. Cadavid has or had stock in Verge Genomics.Dr. Cadavid has or had stock in Vertex Pharmaceuticals.
Stephen Krieger, MD, FAAN (Mount Sinai Dept of Neurology)	Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for EMD Serono. Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Genentech. Dr. Krieger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Novartis. Dr. Krieger has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for TG Therapeutics. Dr. Krieger has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Sanofi. Dr. Krieger has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Cycle. The institution of Dr. Krieger has received research support from Novartis. The institution of Dr. Krieger has received research support from Bristol Myers Squibb. The institution of Dr. Krieger has received research support from Biogen. The institution of Dr. Krieger has received research support from Sanofi.
Helmut Butzkueven, MD, MBBS	Dr. Butzkueven has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Oxford Health Policy Forum. The institution of Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Biogen. The institution of Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for Merck. The institution of Dr. Butzkueven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Novartis. The institution of Dr. Butzkueven has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Roche. Dr. Butzkueven has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for MSBase . The institution of Dr. Butzkueven has received research support from NHMRC. The institution of Dr. Butzkueven has received research support from Biogen. The institution of Dr. Butzkueven has received research support from Roche. The institution of Dr. Butzkueven has received research support from Novartis.
	No disclosure on file
Sha Mi, PhD (Biogenidec)	No disclosure on file

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