When mice with moderate multiple sclerosis were given very low dosages of dextromethorphan, a drug found in cough medicine, the loss of myelin and the development of paralysis during acute attacks was significantly reduced. (Credit: iStockphoto)
UC DAVIS (US) — A drug commonly found in over-the-counter cough medicine may pave the way for a new and inexpensive therapy for multiple sclerosis.
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In animal testing, the drug dextromethorphan significantly reduced the loss of the fatty sheath (or myelin) surrounding nerve fibers in the central nervous system and also minimized development of paralysis during multiple sclerosis attacks.
The study is published online in the journal Neurobiology of Disease.
“This finding provides an exciting opportunity to better understand the disease and to pursue a new treatment strategy with a drug that is widely available, inexpensive, and known to be safe,” says Wenbin Deng, assistant professor of cell biology and human anatomy at University of California, Davis.
Currently there are few effective treatment options for multiple sclerosis, which affects about 400,000 people in the United States and most often first appears in young-to-middle-aged women.
The condition, that has no cure, is caused by cells of the immune system attacking myelin, the fatty sheath surrounding nerve fibers in the central nervous system that speeds the transmission of nerve impulses.
Symptoms vary widely and often involve periods of motor problems, including paralysis of a limb or poor coordination, which unpredictably may either go away or become permanent. As the disease progresses, it causes increasing disability. Many treatments are poorly tolerated and produce a wide range of side effects.
For the new study, investigators induced mice to have either a moderate or severe type of multiple sclerosis and then treated them with either very low or high dosages of dextromethorphan. Very low dosages given to mice with moderate disease significantly reduced the loss of myelin and the development of paralysis during acute attacks. The high dosages did not offer any benefit.
“Finding that a chemical like dextromethorphan might be useful for treating multiple sclerosis is especially significant because we already know it is safe,” says David E. Pleasure, director of research at the Institute for Pediatric Regenerative Medicine at Shriners Hospitals for Children Northern California in Sacramento and one of the authors of the study. “Normally, a possible new treatment must first undergo years of clinical trials to prove this.”
The researchers began investigating common, over-the-counter cough medicines as treatments for devastating diseases like multiple sclerosis because their molecular structure is similar to morphine. Morphinans—low dose morphine-like agents—have been used “off label” for individuals. While they’re not cures, they potentially can be helpful for selected patients, and appear to have little or no toxicity at low doses.
Dextromethorphan is one of a few morphinan drugs similar in structure to morphine, but without the addictive properties. Deng and Pleasure would like to see clinical trials conducted soon to find out if dextromethorphan is effective in humans with multiple sclerosis. Such a trial would likely involve testing in combination with current standard treatment of the disease.
“Dextromethorphan has a different mode of action than current drugs for multiple sclerosis,” Deng says. “While current treatment targets inflammation and the immune system, dextromethorphan appears to be more directly neuroprotective. Combining the different strategies could offer a real breakthrough in fighting the disease.”
The study was supported in part by grants from the National Institutes of Health, National Multiple Sclerosis Society, and Shriners Hospitals for Children.
