Spinal muscular atrophy (SMA) is a severe neurodegenerative condition due to recessive mutations in the SMN1 gene resulting in insufficiency of survival motor neuron (SMN) protein. Lack of SMN protein results in irreversible degeneration of lower motor neurons and consequential muscle atrophy and weakness. SMN2, a SMN1 homologue, produces low levels of functional SMN protein with the potential to partially compensate SMN1 loss. Several compounds have been shown to successfully restore SMN protein production in motor neurons, either by enhancing SMN2 gene function or by direct replacement of the SMN1 gene. Clinical trials of these compounds have demonstrated the potential to substantially alter the natural history of SMA and have led to their implementation into clinical practice. To date, 3 novel drugs, nusinersen, onasemnogene aberparvovec and risdiplam, have received marketing authorisation for SMA treatment by several authorities including Food and Drug Administration and European Medicines Agency. While implementing these drugs into daily clinical practice, clinicians face a number of new challenges, including identifying the most advantageous treatment for any individual, optimisation of outcomes and management of a modified SMA phenotype. Considering that treatment initiation at the pre-symptomatic or paucisymptomatic stage appears to be associated with better outcomes, health services need to support early diagnosis for this now treatable condition. This review aims to give an overview of the current therapeutic landscape of SMA, to provide an understanding of current practice of SMA management and to help increase awareness of the imminent need for urgent early diagnosis at the pre-symptomatic stage.
- child health
Data availability statement
Data sharing not applicable as no datasets generated and/or analysed for this study.
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VLG and MAF-G are joint first authors.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.
Competing interests VLG has received consultancy/speaker honoraria from Novartis, Roche, Biogen, PTC, Pfizer and Sarepta Therapeutics. EW has received consultancy/speaker honoraria from Pfizer, Biogen, Novartis.
Provenance and peer review Commissioned; externally peer reviewed.