New Strategy to Enhance Multiple Sclerosis Treatment and Other Disorders

Working with laboratory mice models of multiple sclerosis (MS), scientists have identified a new molecular target for the design of drugs that could be safer and more effective than current US Food and Drug Administration (FDA)-approved medications against MS.

The research study’s findings, published online May 17, 2013, in the journal EMBO Molecular Medicine could have therapeutic applications for MS as well as cerebral palsy and leukodystrophies, all disorders associated with loss of white matter.

The target, a protein called mitochondrial translocator protein (TSPO), had been earlier identified but not tied to MS, an autoimmune disorder that peels off the protective fatty coating off nerve fibers of the brain and spinal cord. The mitrochronical TSPO is situated on the outer surface of mitochondria, cellular structures that supply energy to the cells. Damage to the fatty coating, or myelin, slows the transmission of the nerve signals that enable body movement as well as sensory and cognitive functioning.

The University of California (UC) Davis (Sacramento, USA) scientists identified mitochondrial TSPO as a potential therapeutic target when mice that had symptoms of MS improved after being treated with the antianxiety drug etifoxine, which interacts with mitochondrial TSPO. When etifoxine, a drug clinically available in Europe, was given to the MS laboratory mice before they had clinical symptoms of disease, the severity of the disease was decreased when compared to the untreated lab animals. When treated at the peak of disease severity, the animals’ MS symptoms improved.

“Etifoxine has a novel protective effect against the loss of the sheath that insulates the nerve fibers that transmit the signals from brain cells,” said Dr. Wenbin Deng, lead investigator of the study and associate professor of biochemistry and molecular medicine at UC Davis. “Our discovery of etifoxine’s effects on an MS animal model suggests that mitochondrial TSPO represents a potential therapeutic target for MS drug development. Drugs designed to more precisely bind to mitochondrial TSPO may help repair the myelin sheath of MS patients and thereby even help restore the transmission of signals in the central nervous system that enable normal motor, sensory and cognitive functions,” he said.

Dr. Deng added that better treatments for MS and other demyelinating diseases are needed, especially since current FDA-approved therapies do not repair the damage of immune attacks on the myelin sheath.

The investigators hope to additionally study the therapeutic applications of mitochondrial TSPO in drug development for MS and other autoimmune disorders. To identify more effective and safer drug candidates, they plan to pursue research grants that will enable them to evaluate a range of pharmacologic agents that bind to mitochondrial TSPO and other molecular targets in research models of MS and other myelin diseases.

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