• Crystal J J Yeo, Eduardo F Tizzano, and Basil T Darras.
• Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA; Department of Neurology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA; School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore; Agency for Science, Technology and Research, Singapore; National Neuroscience Institute, Tan Tock Seng and Singapore General Hospital, Singapore; Duke-NUS Medical School, Singapore.
• Lancet Neurol. 2024 Feb 1; 23 (2): 205218205-218.

AbstractSpinal muscular atrophy was the most common inherited cause of infant death until 2016, when three therapies became available: the antisense oligonucleotide nusinersen, gene replacement therapy with onasemnogene abeparvovec, and the small-molecule splicing modifier risdiplam. These drugs compensate for deficient survival motor neuron protein and have improved lifespan and quality of life in infants and children with spinal muscular atrophy. Given the lifelong implications of these innovative therapies, ways to detect and manage treatment-modified disease characteristics are needed. All three drugs are more effective when given before development of symptoms, or as early as possible in individuals who have already developed symptoms. Early subtle symptoms might be missed, and disease onset might occur in utero in severe spinal muscular atrophy subtypes; in some countries, newborn screening is allowing diagnosis soon after birth and early treatment. Adults with spinal muscular atrophy report stabilisation of disease and less fatigue with treatment. These subjective benefits need to be weighed against the high costs of the drugs to patients and health-care systems. Clinical consensus is required on therapeutic windows and on outcome measures and biomarkers that can be used to monitor drug benefit, toxicity, and treatment-modified disease characteristics.Copyright © 2024 Elsevier Ltd. All rights reserved.

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