A drug withdrawn from pharmacy shelves over 20 years ago may point the way to a new treatment for spinal muscular atrophy, or SMA, a muscle-wasting and often life-threatening childhood disease.
A new study suggests that the drug, called indoprofen, increases the production of a protein that is key to the survival of the nerve cells affected by the disease. Indoprofen was taken off the market in the early 1980s due to reports of serious gastrointestinal reactions as well as reports that the drug caused cancer in laboratory rats.
Researchers are now looking into ways to modify the drug to make it less toxic to humans, said Arthur Burghes, a study co-author and a professor of molecular and cellular biochemistry at Ohio State University.
While SMA strikes only about one in 6,000 newborn Americans each year, it is the leading genetic cause of infant and toddler death in the United States as well as Western Europe. There is no cure or standard treatment, and children with the most severe form of the disease usually die before their second birthday.
Motor neurons – nerve cells that send signals from the spinal cord to muscles throughout the body – rapidly deteriorate in SMA due to reduced levels of survival motor neuron (SMN) protein. Patients with the disease lack SMN1, a gene that produces SMN protein. For reasons that aren't clear, this protein deficiency affects only motor neurons of the spinal cord – all other cells in the body function normally.
SMA patients do have one or more copies of SMN2, a gene that produces low levels of SMN protein. But these levels aren't high enough to stop SMA's deleterious effects on spinal motor neurons. Laboratory experiments using indoprofen to treat human fibroblast cells resulted in a 13 percent increase in SMN protein production in the cells.
"This increase is sort of like giving an additional SMN2 gene to a patient – it would give the patient about 13 to 15 percent more protein," Burghes said. "While this additional protection wouldn't cure the disease, it could lessen the severity of symptoms."
The study appears in the current issue of the journal Chemistry and Biology. Burghes worked with a team of scientists from Columbia University, the National Institutes of Health, the University of Massachusetts Medical School and a hospital in the United Kingdom. Brent Stockwell, the study's principal investigator, is a researcher at Columbia University.