Spinal muscular atrophy (SMA) is an inherited motor-neuron disease that, in its most severe form, leads to death before 2 years of age and for which there is no treatment. It is caused by mutations in the gene SMN1 that prevent SMN1 producing the protein SMN.
A second gene, SMN2, can also produce SMN, but it is much less efficient than SMN1 at doing so. Developing ways to increase SMN production by SMN2 are therefore of potential therapeutic interest.
In a study that appears online on February 22 in advance of publication in the March print issue of the Journal of Clinical Investigation, Charlotte Sumner and colleagues from the NIH show that in a mouse model of SMA a drug known as trichostatin A (TSA) can increase the amount of SMN2 produced SMN in both neural tissues and muscles (the tissues that are affected in humans with SMA). Importantly, daily administration of TSA (which is a hydroxamic acid HDAC inhibitor) to mice already showing signs of SMA-like disease improved their chances of survival and attenuated their disease symptoms. This study therefore provides support for the idea that hydroxamic acid HDAC inhibitors should be developed for the treatment of individuals with SMA.