Researchers Funded by Promise:2010 Find Possible Regulator of Myelin Repair - National Multiple Sclerosis Society

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Researchers Funded by Promise:2010 Find Possible Regulator of Myelin Repair

June 30, 2011

Researchers report that a molecule – called “Axin2” – may be essential to regulating the repair of nerve fiber-insulating myelin, and may be a good target for future therapies aimed at regenerating myelin that has been damaged by the MS disease process. (Myelin is the substance that nourishes and insulates nerve fibers and is damaged in MS). Stephen Fancy, DVM, PhD, David Rowitch, MD, PhD (University of California, San Francisco) and colleagues report on a study co-funded by the National MS Society’s Promise:2010 initiative, the MS Society of the United Kingdom and Northern Ireland, and other funders, in Nature Neuroscience (published online June 26, 2011). This study furthers the Society’s goal of restoring function that has been lost to people with MS, by identifying a possible target for nervous system repair strategies.

Background: The symptoms of MS are caused by faulty nerve signals that are the result of damage to myelin, the material that insulates and protects nerve fibers, and to the nerve fibers themselves. In the brain and spinal cord, myelin is made and maintained by cells known as oligodendrocytes, which are also damaged in MS. Oligodendrocytes develop from progenitor cells, or OPCs; for unknown reasons, these cells often fail to maintain their capacity for myelin repair in people with MS. One goal of MS research is to find ways to stimulate OPCs to make new oligodendrocytes that will repair the damaged myelin.

Previous work by team members has helped to unravel the complex interactions that occur in normal brain development and that may play a role in the repair of myelin that has been damaged by MS (Read more about these studies, here internal link to Jul 13, 2009 news article and here link to Dec 07, 2010 news article) In this study, the team investigated the specific role of Axin2, a key control mechanism of the Wnt pathway, a pathway implicated in myelin repair in their previous work.

The Study: The researchers conducted a series of experiments in mice, as well as in tissue samples isolated via autopsy from human newborns with brain injuries, and from adults with MS. They compared activity levels of the gene Axin2, and found that the gene was active in oligodendrocytes in newborns with brain injury, but not in normal newborn brain tissue. They also found that the Axin2 gene was active in oligodendrocytes in areas of inflammation in people with MS, but not in tissue that appeared normal.

Mice genetically engineered lacking the Axin2 gene showed a delay in both developmental myelin formation and myelin repair after injury as adults, and Axin2 seemed to be important in controlling the timing of oligodendrocyte maturation during these processes. The group also found evidence that a chemical called XAV939 could increase the levels of Axin2 in oligodendrocytes, by preventing it from degrading, and this led to an acceleration of myelin repair in mice.

Comment: These findings, co-funded through the National MS Society’s Promise:2010 Nervous System Repair and Protection Initiative, point out a potential target for the development of a therapy that may reverse MS myelin damage and restore function. As noted by the authors, further research is needed to confirm the findings and to determine the safety and effectiveness of agents such as XAV939 in stabilizing Axin2 and promoting myelin repair.

Read more about the Promise:2010 Nervous System Repair and Protection Initiative that co-funded this study.

About Multiple Sclerosis

Multiple sclerosis, an unpredictable, often disabling disease of the central nervous system, interrupts the flow of information within the brain, and between the brain and body. Symptoms range from numbness and tingling to blindness and paralysis. The progress, severity and specific symptoms of MS in any one person cannot yet be predicted, but advances in research and treatment are moving us closer to a world free of MS. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease. MS affects more than 2.3 million people worldwide.

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