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The purpose of this study was to identify the molecular target of the human monoclonal antibody HIgM12. HIgM12 reverses motor deficits in chronically demyelinated mice, a model of MS. Here we identified polysialic acid (PSA) attached to the Neural Cell Adhesion Molecule (NCAM) as the antigen for HIgM12 by using different NCAM knockout strains and through PSA removal from the NCAM protein core. Antibody binding to CNS tissue and primary cells, antibody-mediated cell adhesion and neurite outgrowth on HIgM12-coated nitrocellulose was detected only in the presence of PSA as assessed by Western blotting, immunoprecipitation, immunocytochemistry and histochemistry. We conclude that HIgM12 mediates it's in vivo and in vitro effects through binding to PSA and has the potential to be an effective therapy for MS and neurodegenerative diseases
Via Krishan Maggon
Watzlawik JO, Kahoud RJ, Ng S, Painter MM, Papke LM, Zoecklein L, Wootla B, Warrington AE, Carey WA, Rodriguez M. Polysialic Acid as an Antigen for Monoclonal Antibody HIgM12 to Treat Multiple Sclerosis and Other Neurodegenerative Disorders.J Neurochem. 2015. doi: 10.1111/jnc.13121. [Epub ahead of print]
American Academy of Neurology Annual Meeting 2015 AAN 2015