What Genetics Has Told Us and How It Can Inform Future Experiments for Spinal Muscular Atrophy, a Perspective

Proximal spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disorder characterized by motor neuron loss and subsequent atrophy of skeletal muscle. SMA is caused by deficiency of the essential survival motor neuron (SMN) protein, canonically responsible for the assembly of the spliceosomal small nuclear ribonucleoproteins (snRNPs). Therapeutics aimed at increasing SMN protein levels are efficacious in treating SMA. However, it remains unknown how deficiency of SMN results in motor neuron loss, resulting in many reported cellular functions of SMN and pathways affected in SMA. Herein is a perspective detailing what genetics and biochemistry have told us about SMA and SMN, from identifying the SMA determinant region of the genome, to the development of therapeutics. Furthermore, we will discuss how genetics and biochemistry have been used to understand SMN function and how we can determine which of these are critical to SMA moving forward.

Automated summary

Proximal spinal muscular atrophy (SMA) is a genetic disorder characterized by motor neuron loss and skeletal muscle atrophy due to deficiency of the essential survival motor neuron (SMN) protein. Therapeutics aimed at increasing SMN protein levels have shown efficacy in treating SMA, but the mechanisms underlying motor neuron loss are still not well understood. Genetics and biochemistry have provided insights into SMA and SMN, from identifying genetic regions to developing potential treatments, but further research is needed to determine critical pathways in SMA.