Collaborative MS Research Center Award
||Rhonda Voskuhl, MD
University of California
Los Angeles, CA
Arthur Toga, PhD
Michael Sofroniew, MD, PhD
Leif Havton, MD, PhD
Nancy Sicotte, MD
Barbara Giesser, MD
University of California, Los Angeles, CA
Using cutting-edge techniques to characterize the nerve fiber damage that occurs in MS and developing candidates for neuroprotective therapies.
Current therapies for MS reduce relapses, but their long-term influence on the development of permanent disability is unclear. Consequently, there is a great need to find strategies to protect nerve fibers in MS which could potentially be used in combination with anti-inflammatory therapies. Research indicates that disability in MS correlates less with the loss of nerve fiber-insulating myelin, and more with the loss of nerve fibers and cells themselves.
Developing neuroprotective strategies in MS requires a better understanding of how nerve cells are damaged in this disease. Exploring neurodegeneration in the MS-like disease EAE and searching for neuroprotective strategies are the goals of a Collaborative MS Research Center with unique and powerful capabilities. Leading the group is Dr. Rhonda Voskuhl, a former National MS Society Harry Weaver Neuroscience Scholar, whose groundbreaking research efforts have involved investigating the role of sex hormones in providing protection from EAE, and then translating this work into clinical studies of these hormones in people with MS.
Co-investigator Dr. Leif Havton, an investigator in the field of neuroprotection, is studying nerve tissue damaged in EAE using advanced molecular techniques that have borne fruit in the field of spinal cord injury. He is investigating damage that occurs "beyond the lesion" (beyond the area where inflammation and tissue damage are evident) using electron microscopy. These studies will help determine the extent of nerve fiber loss in EAE, and how it affects function. Dr. Arthur Toga will apply cutting-edge neuroimaging analysis to abnormalities spotted by Dr. Havton. Dr. Toga recently developed a powerful tool to assess tissue loss in the brain and spinal cord of mice in specifically delineated regions. The tool is a "digital atlas" of a mouse brain, and has been deemed extremely important for nervous system research in mice.
Drs. Michael Sofroniew and Voskuhl will collaborate to examine the role of star-shaped brain cells called "astrocytes" in nerve cell degeneration in EAE. Dr. Sofroniew has developed a mouse model in which the actions of astrocytes can be examined specifically, and has used this model to show that removing astrocytes during spinal cord injury causes a significantly greater loss of nerve cells than if these cells were not removed.
Dr. Voskuhl has found that pregnancy levels of estrogens ameliorate EAE and are anti-inflammatory. She will now begin determining whether estrogen treatment can also be neuroprotective in EAE using the mouse models developed by Dr. Sofroniew and the methods of Drs. Havton and Toga.
The group will also design a pilot clinical trial of the most promising agents identified in Dr. Voskuhl's studies. Dr. Barbara Giesser is Director of the UCLA MS Achievement Center (MSAC), a Society-sponsored rehabilitation center in MS. She will draw upon resources in the MSAC in assessing, and possibly promoting, the effectiveness of neuroprotective treatments under study. Joining the team is National MS Society Harry Weaver Neuroscience Scholar Dr. Nancy Sicotte, who is applying advanced imaging techniques in collaboration with Dr. Toga to determine how specific "markers" identified with these techniques can be used to monitor the success of neuroprotective treatment in these trials.
This interdisciplinary team, which brings to the table expertise in basic neuroscience, basic neuroimaging, immunology, and clinical MS, is poised to achieve its goal of finding ways to protect brain tissues and preserve function in persons with MS.