Multiple Sclerosis Research Focuses on Axons
Dr. James Garbern has uncovered some good news and some bad news in multiple sclerosis (MS) research. The good news is a novel approach to studying the disease. Previously, researchers thought of MS as a disease that exclusively affected myelin, the membranes surrounding axons, which are the nerve fibers connecting different parts of the nervous system. New evidence shows that the disease actually destroys the axons themselves. This information allows Dr. Garbern to attack the problem from a new front. The bad news is that there are no current therapies to repair axonal damage, so new treatment regimens need to be developed to prevent or slow this process.
With support from the National Multiple Sclerosis Society, Dr. Garbern is studying “Animal Models of Axonal Injury Due to Myelin Disorders.” As he explains, axons are nerve fibers that may be attacked directly by the immune system or secondarily by damage to oligodendrocytes, the cells in the central nervous system (CNS) that make myelin. Not knowing the cause of MS, however, makes it very difficult to know the cause of axonal damage.
Dr. Garbern will study mice that have mutations in the gene that encodes the most abundant CNS myelin protein, proteolipid protein (PLP). Mice with particular PLP mutations develop axonal degeneration, even though PLP is made not in neurons, or nerve cells, but by oligodendrocytes. This demonstrates that a disturbance in oligodendrocyte function can cause axonal damage.
Using magnetic resonance spectroscopy (MRS), Dr. Garbern, in collaboration with Dr. Gregory Moore and other members of the brain imaging program, will track the development of axonal damage in these mice by measuring drops in the concentration of N-acetyl aspartate (NAA), a chemical that is specific to axons. Reduced NAA levels are believed to indicate axonal damage and neurologic disability. By correlating different PLP mutations with the degree of axonal injury they cause, Dr. Garbern and his colleagues hope to develop a better understanding of PLP function and to refine the application of MRS and other magnetic resonance technologies to the study of neurodegenerative diseases.
“Discovering the signals between oligodendrocytes and axons may lead to the development of new treatments that could delay or prevent axonal damage in MS patients as well as in patients with other myelin diseases,” he said.
James Garbern, MD, PhD, is an assistant professor in neurology and the Center for Molecular Medicine. His other primary research interests include molecular biology of myelin disorders, molecular pathogenesis of glial tumors and Pelizaeus- Merzbacher Disease, which is caused by mutations of the human PLP gene.