Friday, 24 April 2015

The target for a remyelinating antibody is NCAM

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]

CNS regeneration is a desirable goal for diseases of brain and spinal cord. Current therapeutic strategies for the treatment of multiple sclerosis (MS) aim to eliminate detrimental effects of the immune system, so far without reversing disability or affecting long-term prognosis in patients. Approachable molecular targets that stimulate CNS repair are not part of the clinical praxis or have not been identified yet. 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


HIgM12 is said to be a a remyelinating antibody. The question is how does this work. In this study they show that HIgM12 binds to . Polysialic acid. This is an unusual posttranslational modification that occurs on neural cell adhesion molecules (NCAM). Polysialic acid is considerably anionic. This strong negative charge gives this modification the ability to change the protein's surface charge and binding ability. In the synapse, polysialation of NCAM prevents its ability to bind to NCAM's on the adjacent membrane. It is also thought to abrogate its homophilic binding properties and can lead to reduced cell adhesion important in cell migration and invasion Maybe this is how it works

1 comment:

  1. I know it's too early to talk about "comparative" but in "thesis" would be meaningless efficiency compared to anti lingo-1?

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