Our laboratory is focused on determining the mechanisms of demyelination and remyelination in diseases such as human multiple sclerosis through primary animal models of demyelination. We are investigating the mechanisms of neurological deficits following demyelination. One major focus of the laboratory is to understand the immunogenetics of demyelination. We are studying the role of specific Theiler's viral capsid proteins in resistance versus susceptibility. We have now generated a series of transgenic mice that will enable us to study the development of demyelination and neurological deficits.
The laboratory is particularly interested in developing strategies to promote remyelination in the central nervous system. Having observed that immunization of Theiler's virus-infected mice with spinal cord homogenate induces remyelination, we subsequently showed that transfer of immunoglobulins directed against spinal cord into animals chronically infected with Theiler's virus induces remyelination. As a result, we generated a series of monoclonal antibodies that promote remyelination. These antibodies are directed against surface components on oligodendrocytes. Most recently, we have generated two human monoclonal antibodies that also bind to the surface of rat and human oligodendrocytes which also promote remyelination in both the Theiler's virus system and the lysolecithin model system. Molecular sequences of these antibodies are now characterized under the direction of Dr. Pease. The goal is to begin to develop these antibodies for clinical trials to enhance remyelination in multiple sclerosis.