In the past decade major advances have been made in the treatment of spinal muscular atrophy, a devastating, progressive motor neuron disease caused by a deficiency in the SMN protein due to a mutation in the SMN1 gene. Several approaches aimed at increasing production of the SMN protein have been developed. The intra-thecal antisense oligonucleotide nusinersen and an oral small molecule risdiplam (approved by the US Food and Drug Administration and the European Medicines Agency) target splicing of the paralogous gene SMN2, hence improving the production of the functional SMN protein. Onasemnogene abeparvovec is a one-time AAV-9-based gene transfer therapy, introducing a full copy of the SMN1 gene. Approval was based on data from the START study,1 reporting an unprecedented survival rate at 24 month follow-up and unexpected acquisition of motor milestones in 12 patients with infantile-onset spinal muscular atrophy type 1, the most severe type of the disease, which is characterised by a poor prognosis with short life expectancy.
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