Researchers have pinpointed a molecule – called “Contactin-1” – that is crucial to the formation of the myelin coating along nerve fibers which is damaged in MS, and which represents a novel target for developing strategies for repairing myelin to restore function in people with MS. Barbara Ranscht, PhD (Sanford-Burnham Institute for Medical Research, La Jolla, CA) and colleagues in California and Sweden report their findings in Proceedings of the National Academy of Sciences USA (Early online publication, January 2, 2014). This project was supported by the National MS Society, with other support from the National Institutes of Health and the Sweden-America Foundation.
Reversing damage to regain function through nervous system and myelin repair is a priority of the National MS Society’s research efforts to find solutions for everyone who has MS.
Background: Myelin is a supportive casing that surrounds nerve fibers (axons) and speeds nerve conduction. Myelin is damaged during immune attacks on the brain and spinal cord in MS, and so are the cells that make myelin, called oligodendrocytes. The growth of myelin and its proper function require continuous “cross-talk” between oligodendrocytes and the axons they wrap with myelin. Understanding the molecular language of this communication is critical for identifying molecular targets for new treatments aimed at both protecting myelin in MS and enhancing its repair.
Barbara Ranscht, PhD, is studying Contactin-1, a cell surface molecule on axons and oligodendrocytes that has emerged as a key signal involved in their communication during myelin formation. Her team has generated a new mouse model that allows teasing out of Contactin-1’s role.
The Study: Dr. Ranscht and colleagues examined Contactin-1 activity in the developing nervous system in mice, to determine its effects on myelin formation. They also examined mice in which this molecule was genetically deleted, to determine what effects there would be on myelin formation.
In the developing nervous system, the team observed that Contactin-1 was active on myelin-making cells, and also along axons in the area of nodes – clusters of specifically organized proteins that are crucial to nerve impulse conduction. Myelin formation significantly decreased in mice lacking Contactin-1, and the organization of nodes and wrapping of the myelin sheath around axons was dramatically disrupted.
Conclusions: These studies pinpoint the molecule Contactin-1 as an important player in myelin growth and axon health, and may represents a novel target for the development of potential strategies that might repair damage to the nervous system and restore function to people with MS. Additional basic research is needed to further develop these findings. “It is now critical to determine the specific molecular mechanisms by which Contactin-1 regulates the remarkable cellular assembly that constitutes myelin, and evaluate its potential for myelin repair in the central nervous system,” write the authors.
Read more about research to repair damaged tissue in MS.