A deep dive into spinal muscular atrophy: Causes, progression, and genetic therapies

Spinal muscular atrophy (SMA) is a motor neuron disorder characterized by the typically progressive weakness and atrophy of muscles corresponding to the lower motor neuron with early onset. SMA is caused by the loss of function of insufficient levels of the SMN protein due to homozygous deletions or defects in the SMN1 gene, an essential housekeeping gene usually found in two copies in the genome. However, the surviving SMN2 gene, which only produces low levels of the SMN protein, modulates the disease severity and symptoms. Historically, SMA has been classified into types based on the age at onset and the highest motor milestones achieved, ranging from typically lethal SMA type I to the milder-form SMA type IV, with three intermediate types. Moreover, SMA is classified as a lower motor neuron disorder with an exclusively neurological phenotype.