A Wayne State University School of Medicine researcher has secured a $700,000 grant from the National Multiple Sclerosis Society of America to develop a mouse model that could lead to testing of new drugs to treat stress that can exacerbate MS.
Alexander Gow, Ph.D., associate professor in the School of Medicine's Center for Molecular Medicine and Genetics, the Carman and Ann Adams Department of Pediatrics, and the Department of Neurology, will use the four-year grant to generate a non-immune animal model of multiple sclerosis.
Because MS and similar diseases do not occur in animals, Dr. Gow said, researchers must first establish an animal model with a weakened immune system for testing. Once the animal model is established, Dr. Gow can use the mice to determine how the disease gets started, study its pathology and then design drugs to alleviate the symptoms.
MS is considered an autoimmune disease. The body's own immune system attacks the brain and gradually destroys it, typically over many years.
"An obvious treatment for such a disease is to suppress the immune system so it won't attack the brain," Dr. Gow explained, "and such a treatment is in common use, using steroids. This treatment does improve the disease symptoms, but only in the short term. The long-term prognosis is unchanged."
Since immune suppression is not a cure, Dr. Gow's lab has been investigating metabolic stress as a factor in the disease process. He said there is "good evidence" that cells in the brain damaged by MS - cells called oligodendrocytes - experience the stress. Dr. Gow is studying a mouse with a genetic mutation that causes metabolic stress in oligodendrocytes. His lab has been characterizing the effect of stress on the cells, and has engineered a new gene into the Rumpshaker Mutant Mouse (RSH). The Trb3 gene appears to relieve the stress, and RSH mice that also have the gene show milder disease symptoms than RSH mice without that gene.
The National Multiple Sclerosis Society of America grant will allow Dr. Gow's lab to complete the characterization of the mice and determine the biological function of the Trb3 gene.
"This is an important study to investigate whether MS causes myelin-making cells to self-destruct, and if so, find ways to block this process," said Dr. Patricia A. O'Looney, vice president of Biomedical Research for the National Multiple Sclerosis Society.
Once he determines the biological function of the Trb3 gene in oligodendrocytes, "we will probably know how this gene reduces the disease symptoms of RSH mice," Dr. Gow explained. "Next, we will look for drugs that mimic the activity of the Trb3 gene and use them on the RSH mice. If those tests identify useful drugs, we will be in a position to begin pre-clinical trials for MS."
Eventually, Dr. Gow said, he hopes that the drugs identified as reducing oligodendrocyte stress in the mice can then be tested in MS patients.
"Because there are no similar approaches to MS treatments, the drugs may move fairly rapidly through the trial process," he said. "We will focus on drugs that are already in pre-clinical or clinical trials, which should move the drug trials along fairly quickly.
"I can't overemphasize the timeliness of these grants for our work. We are on the verge of significant advances in these diseases, but federal government policies toward medical research over the last four to six years have been so harsh that it has become very difficult to continue research on rare diseases," Dr. Gow said. "The National Institutes of Health simply has insufficient funds to support such research."