Challenges and opportunities in clinical trials for spinal muscular atrophy.

Spinal muscular atrophy (SMA) is the most common fatal neuromuscular disease of infancy. SMA type I is the most severe and mortality is usually due to respiratory failure. In type II the disability is of later onset and less severe, and prognosis has improved primarily due to supportive care. Type III is the mildest form with onset usually of weakness in adolescence or young adulthood. SMA is an autosomal recessive disorder with deletions or mutations of the gene at the 5 q11 locus. There is no specific prevention or treatment, but current progress toward potential therapies has been substantial and several candidates including histone deacetylase (HDAC) inhibitors are under consideration for further evaluation. The authors sought to address the challenges and opportunities for testing new therapies for SMA.