Learning to walk

Spinal muscular atrophy (SMA) is a genetically determined neuronopathy and usually presents in childhood. SMA has a broad range of phenotypes: severe early infancy onset (type I, Werdnig-Hoffman disease, non-sitters), later infancy onset, intermediate variety (type II, sitters, non-walkers), and childhood to adulthood onset (type III, Kugelberg-Welander, walkers).^1,2 In addition to progressive limb and truncal weakness, dysphagia, aspiration, and respiratory insufficiency are predictable life-threatening comorbidities of the infantile type I and II forms.³ As yet, no effective drug therapy has been found for human SMA.

Advances in molecular genetics led to the discovery of the causative mutation in the Survival Motor Neuron (SMN) 1 gene and elucidation of the rescue of an otherwise lethal condition by a nearly identical homologue gene, SMN2.⁴ The number of copies of this SMN2 gene is inversely associated with disease severity, and this gene dosing observation has led to treatment strategies targeting SMN2.⁵ These strategies for SMA include induction of SMN2 gene expression, modulation of splicing of SMN2-derived transcripts, and stabilization …