{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:31:55Z","timestamp":1792812715936,"version":"4.5.0"},"reference-count":57,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"UK Department of Health and Social Care","award":["C72219"],"award-info":[{"award-number":["C72219"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJNS"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) causes the degeneration of motor neurons in the spinal cord. Treatments including nusinersen, risdiplam, and onasemnogene abeparvovec have been shown to be effective in reducing symptoms, with recent studies suggesting greater effectiveness when treatment is initiated in the presymptomatic stage. This systematic review synthesises findings from prospective studies of presymptomatic treatment for 5q SMA published up to December 2023. The review identified three single-arm interventional studies of presymptomatic treatment (NURTURE, RAINBOWFISH, and SPR1NT), six observational studies comparing presymptomatic or screened cohorts versus symptomatic cohorts, and twelve follow-up studies of screened cohorts only (i.e., babies identified via newborn screening for SMA). Babies with three SMN2 copies met most motor milestones in the NURTURE study of nusinersen and in the SPR1NT study of onasemnogene abeparvovec. Babies with two SMN2 copies in these two studies met most motor milestones but with some delays, and some required ventilatory or feeding support. The RAINBOWFISH study of risdiplam is ongoing. Na\u00efve comparisons of presymptomatic treatment in SPR1NT, versus untreated or symptomatic treatment cohorts, suggested improved outcomes in patients treated presymptomatically. Comparative observational studies supported the finding that presymptomatic treatment, and early treatment following screening, may improve outcomes compared with treatment at the symptomatic stage. Further research should assess the long-term clinical outcomes and cost-effectiveness of presymptomatic treatment for SMA.<\/jats:p>","DOI":"10.3390\/ijns10030056","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T10:28:41Z","timestamp":1723631321000},"page":"56","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Systematic Review of Presymptomatic Treatment for Spinal Muscular Atrophy"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7702-8103","authenticated-orcid":false,"given":"Katy","family":"Cooper","sequence":"first","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield, Sheffield S1 4DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamze","family":"Nalbant","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield, Sheffield S1 4DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthea","family":"Sutton","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield, Sheffield S1 4DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue","family":"Harnan","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield, Sheffield S1 4DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praveen","family":"Thokala","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield, Sheffield S1 4DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1231-7817","authenticated-orcid":false,"given":"Jim","family":"Chilcott","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield, Sheffield S1 4DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alisdair","family":"McNeill","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield, Sheffield S1 4DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7677-0309","authenticated-orcid":false,"given":"Alice","family":"Bessey","sequence":"additional","affiliation":[{"name":"School of Medicine and Population Health, University of Sheffield, Sheffield S1 4DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.tins.2020.11.009","article-title":"Spinal Muscular Atrophy: In the Challenge Lies a Solution","volume":"44","author":"Wirth","year":"2021","journal-title":"Trends Neurosci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1002\/ajmg.a.30251","article-title":"Homozygous SMN1 Deletions in Unaffected Family Members and Modification of the Phenotype by SMN2","volume":"130","author":"Prior","year":"2004","journal-title":"Am. 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