Research discovers a molecular switch for repairing CNS disorders

Mayo Clinic research has determined that a molecular switch can turn on a substance in animals that repairs neurological damage in disorders such as multiple sclerosis (MS). Early research in animal models could advance an already-approved Food and Drug Administration therapy and lead to new strategies to treat diseases of the central nervous system.

Research by Isobel Scarisbrick, Ph.D. (BIOC ’96), published in the Journal of Neuroscience, found that by genetically switching off a receptor activated by blood proteins, named Protease Activated Receptor 1 (PAR1), the body switches on regeneration of myelin.

“Myelin regeneration holds tremendous potential to improve function,” says Dr. Scarisbrick, the principal invstigator. “We showed when we block the PAR1 receptor, neurological healing is much better and happens more quickly. In many cases, the nervous system has a good capacity for innate repair. This sets the stage for development of new clinically relevant myelin regeneration strategies.”

The research focused on two mouse models. One was an acute model of myelin injury, and the other studied chronic demyelination, each modeling unique features of myelin loss present in MS, Alzheimer’s disease and other neurological disorders. Researchers genetically blocked PAR1 to block the action of excess thrombin.

The research not only discovered a new molecular switch that turns on myelin regeneration but also discovered a new interaction between the PAR1 receptor and a very powerful growth system called brain derived neurotropic factor (BDNF). BDNF is like a fertilizer for brain cells that keeps them healthy, functioning and growing.

Researchers found that a current FDA-approved drug that inhibits the PAR1 receptor also showed ability to improve myelin production in cells tested in the laboratory.

“We have not yet used the drug in animals, and it is not ready to put in patients for the purpose of myelin repair,” says Dr. Scarisbrick. “Using cell culture systems, we are showing that this has the potential to improve myelin regeneration.”