Wayne State University awarded grant to explore new MS pathology model

The National Multiple Sclerosis Society has provided a grant to a Wayne State University School of Medicine professor to explore a new model of MS pathology.

Alexander Gow, Ph.D., the Charles H. Gershenson Distinguished Fellow Professor and associate director of the WSU Center for Molecular Medicine and Genetics, will use the three-year, $663,959 grant for his study, "Neurodegeneration associated with metabolic stress in oligodendrocytes."

From the early-mid phases of MS, Dr. Gow said, the clinical symptoms are caused by considerable damage to the brain in the forms of autoimmune lesions, atrophy in the white matter and gray matter of the brain and cognitive deficits. Most studies to date have focused on finding disease-modifying therapies for the autoimmune component of MS, but have tended to ignore the cognitive changes, which can be the most debilitating and frustrating aspects for patients and caregivers.

Several important findings have come to light in recent years, he said, including the revelation that strong immunosuppression of patients for several years only modestly slows MS progression while damage to cortical brain regions continues and is widespread.

"In this study, we tackle both of these issues using a new model of MS pathology that does not involve autoimmune stimulation to generate disease symptoms," said Dr. Gow, who also is a professor of Pediatrics and of Neurology for WSU. "Rather, we activate metabolic stress in oligodendrocytes to cause dysfunction and death of these cells, which is a potential disease mechanism that has gained experimental support from several laboratories."

Oligodendrocytes are a type of cell that produce a membrane called myelin that coats axons, the pathways by which the brain sends messages to the muscles.

Dr. Gow will seek to determine whether this nonimmune-mediated animal model can recapitulate MS pathology and whether he can find evidence for behavioral changes and cognitive decline. He also will test a drug treatment designed to protect oligodendrocytes and neurons from the degenerative changes associated with inducing primary metabolic stress.

There is increasing evidence, Dr. Gow said, to indicate that autoimmune attacks on the central nervous system may be a secondary event rather than the primary cause of MS. This indicates that researchers must cast a broader net to test new ideas and develop alternative models that could shed fresh light on MS etiology.