Moses Rodriguez1,2, Allan Bieber1, Art Warrington1, Virginia Van Keulen2, Bogoljub Ciric2, Larry Pease2. Departments of Neurology1 and Immunology2, Mayo Medical and Graduate Schools, Rochester, MN 55905

Promotion of CNS remyelination remains an important goal for the treatment of multiple sclerosis. Our laboratory has proposed the use of immunoglobulins directed at CNS antigens as an approach to enhance repair. We have identified a panel of monoclonal antibodies which promote remyelination in virus-induced, autoimmune and toxic models of demyelination in mice. These antibodies react to surface antigens on oligodendrocytes, are primarily of the IgM isotype, and show relatively non-mutated immunoglobulin variable region sequences comparable to germ line. We are testing two major hypothesis to explain the mechanism of antibody- mediated myelin repair. The direct hypothesis proposes that antibodies react to surface antigens on oligodendrocytes to induce differentiation and/or proliferation of these cells. The Indirect hypothesis proposes that antibodies bind to injured myelin and/or oligodendrocytes resulting in more efficient scavenging by macrophages thus allowing endogenous repair to take place. This approach to enhance repair is readily applicable to clinical trials in patients with CNS demyelination or injury.