1. Cellular mechanisms of central nervous system repair by natural autoreactive monoclonal antibodies.
- Author
-
Wright BR, Warrington AE, Edberg DD, and Rodriguez M
- Subjects
- Animals, Antibodies, Monoclonal metabolism, Autoantibodies metabolism, Autoantigens immunology, Autoantigens metabolism, Central Nervous System immunology, Central Nervous System metabolism, Central Nervous System pathology, Humans, Multiple Sclerosis immunology, Multiple Sclerosis metabolism, Multiple Sclerosis therapy, Antibodies, Monoclonal physiology, Antibodies, Monoclonal therapeutic use, Autoantibodies physiology, Autoantibodies therapeutic use, Multiple Sclerosis pathology
- Abstract
Natural autoreactive monoclonal IgM antibodies have demonstrated potential as therapeutic agents for central nervous system (CNS) disease. These antibodies bind surface antigens on specific CNS cells, activating intracellular repair-promoting signals. IgM antibodies that bind to surface antigens on oligodendrocytes enhanced remyelination in animal models of multiple sclerosis. IgM antibodies that bind to neurons stimulate neurite outgrowth and prevent neuron apoptosis. The neuron-binding IgM antibodies may have utility in CNS axon- or neuron-damaging diseases, such as amyotrophic lateral sclerosis, stroke, spinal cord injury, or secondary progressive multiple sclerosis. Recombinant remyelination-promoting IgM antibodies have been generated for formal toxicology studies and, after Food and Drug Administration approval, a phase 1 clinical trial. Natural autoreactive monoclonal antibodies directed against CNS cells represent novel therapeutic molecules to induce repair of the nervous system.
- Published
- 2009
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