New insight into a therapeutic approach to treating SMA

Spinal muscular atrophy (SMA) is the most frequently inherited cause of infant mortality. Two independent research groups — one led by Alex MacKenzie, at Children's Hospital of Eastern Ontario Research Institute, Ottawa; and one led by Umrao R. Monani, at Columbia University Medical Center, New York, and Cathleen M. Lutz, at The Jackson Laboratory, Bar Harbor — have now generated new data in mouse models of severe SMA that provide hope that a therapeutic providing meaningful benefit to individuals with SMA can be developed. SMA is caused by mutations in the SMN1 gene that reduce levels of SMN protein, leading to loss of nerve cells in the brain stem and spinal cord that control muscles. This, in turn, leads to skeletal muscle weakness, wasting, and premature death. Increasing levels of SMN protein in individuals with SMA is considered a viable therapeutic option.

In the first study, MacKenzie and colleagues find that prolactin treatment increases SMN levels, improves muscle movement, and enhances survival in a mouse model of severe SMA. As prolactin has been used in the clinic to augment lactation in mothers of preterm infants, this drug has more immediate therapeutic potential than other drugs that do the same but have no history of safety in humans.

In the second study, Monani, Lutz, and colleagues find that increasing levels of SMN protein after disease onset in a mouse model of severe SMA has therapeutic benefit. These data raise the possibility that treatments designed to increase SMN levels could be effective, even if initiated at relatively advanced stages of the disease.

Kathryn Swoboda, at the University of Utah, Salt Lake City, discusses in detail these two reports and their therapeutic implications in an accompanying commentary.

Source: Journal of Clinical Investigation