Curing SMA: Are we there yet?

Abstract

Loss or deletion of survival motor neuron 1 gene (SMN1) is causative for a severe and devastating neuromuscular disease, Spinal Muscular Atrophy (SMA). SMN1 produces SMN, a ubiquitously expressed protein, that is essential for the development and survival of motor neurons. Major advances and developments in SMA therapeutics are shifting the natural history of the disease. With three relatively new available therapies, nusinersen (Spinraza), onasemnogene abeparvovec (Zolgensma), and risdiplam (Evrysdi), patients survive longer and have improved outcomes. However, patients and families continue to face many challenges associated with use of these therapies, including poor treatment response and a variability in the benefits to those that do respond, suggesting that the quest for the SMA cure is not over. In this review, we discuss the current therapies, their limitations, and highlight necessary gaps that need to be addressed to guarantee the best outcomes for SMA patients.