A pair of recent studies is providing insight into the underlying mechanisms of multiple sclerosis (MS).1,2 These discoveries and others like them could help shed light on the unknowns behind the disorder and lead to better treatments for patients someday.
It's estimated that approximately 400,000 Americans have MS, and each week, about 200 people are diagnosed.
Specifically, researchers have uncovered the processes surrounding the formation of myelin—the fatty substance that insulates nerve fibers in the central nervous system and which is thought to play a key role in the development of MS. These clues may help experts looking for ways to repair tissue damage that is characteristic of the disease, say the investigators.
Immune Attack Gone Awry
Multiple sclerosis is a disease of the central nervous system, disrupting communication between the brain and other parts of the body. Many experts believe it is an autoimmune disease, in which the immune system launches a defensive attack against its own tissues. In this scenario, it is myelin that comes under attack.
Initial symptoms most often occur in people between the ages of 20 and 40; they can manifest as blurred or double vision, red/green color distortion, double vision, or even blindness in one eye. Later, symptoms may range from muscle weakness in the extremities to partial or complete paralysis.3
Origins of Myelin Production Probed
In the first study,1 doctors at the University of Texas Southwestern Medical Center in Dallas assessed the role of a gene that was previously known to initiate the development of oligodendrocytes (ah-lih-goh-DEN-droh-sites), cells that make myelin. A previous study unveiled this past December by researchers at the Dana-Farber Cancer Institute at Harvard University linked the gene to myelin repair for the first time.4
In the latest research involving a group of mice, rodents that lacked the gene did not produce myelin, and they "develop severe neurological deficits and die in the third postnatal week," wrote Richard Lu, PhD, a postdoctoral researcher, and his colleagues.
However, in these deficient animals, the initial steps of myelin formation did occur, in which oligodendrocytes reach out to and make contact with nerve fibers. Despite this, Lu's team eventually saw widespread and progressive loss of nerve fibers in the mice, and though myelin did form in the animals' spinal cords, it was at a greatly reduced rate.
In conclusion, Lu and his colleagues determined that the gene is a major regulator of myelin formation in the brain and that there are separate phases of myelin formation that are controlled by various genes.
What Causes Myelin Problems in MS?
In a separate study,2 doctors at Hôpital de la Salpetriere in Paris believed they uncovered a key to why myelin repair often fails after MS strikes. They studied the role of a receptor on oligodendrocytes. Receptors are molecules on cells that, when activated by a certain substance in the body like proteins, creates a physiologic effect. The study team, headed by neurologist Catherine Lubetzki, MD, PhD, discovered that activating the receptor induced immature myelin-producing cells to move back from nerve fibers in the central nervous systems of a group of mice. This process prevented the immature oligodendrocytes from maturing and launching the process of producing myelin. But simultaneously, this same receptor promoted the survival of mature oligodendrocytes.
If future studies confirm that the receptor is a key factor in preventing immature oligodendrocytes from maturing and forming new myelin after an MS attack, this knowledge may help devise strategies to promote the development of oligodendrocytes for myelin repair, Lubetzki and her team noted.
1. Xin M, Yue T, Ma Z, Wu FF, Gow A, Lu QR. Myelinogenesis and axonal recognition by oligodendrocytes in brain are coupled in Olig1-null mice. J Neurosci 2005 Feb 9;25(6):1354-65.
2. Jaillard C, Harrison S, Stankoff B et al. Edg8/S1P5: an oliogdendroglial receptor with dual function on process retraction and cell survival. J Neurosci 2005 Feb 9;25(6):1459-69.
3. National Institute of Neurological Disorders and Stroke. National Institutes of Health (NIH). Available at: http://www.ninds.nih.gov/disorders/multiple_sclerosis/multiple_sclerosis.htm. Accessed March 24, 2004.
4. Arnett HA, Fancy SP, Alberta JA et al. bHLH transcription factor Olig1 is required to repair demyelinated lesions in the CNS. Science 2004 Dec 17;306(5704):2111-5.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include coverage of health news for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
