{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:42:04Z","timestamp":1790109724463,"version":"4.0.1"},"reference-count":47,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,10]],"date-time":"2023-10-10T00:00:00Z","timestamp":1696896000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>Spinal muscular atrophy (SMA) is a rare neuromuscular disease, with an estimated incidence of about 1 in 10,000 live births. To date, three orphan drugs have been approved for the treatment of SMA: nusinersen, onasemnogene abeparvovec, and risdiplam. The aim of this narrative review was to provide an overview of the pre- and post-marketing evidence on the pharmacological treatments approved for the treatment of SMA by identifying preclinical and clinical studies registered in clinicaltrials.gov and in the EU PAS register from their inception until the 4 January 2023. The preclinical evidence on the drugs approved for SMA allowed a significant acceleration in the experimental phase of these drugs. However, since these drugs had been authorized through accelerated programs, the conduction of post-marketing studies was requested as a condition of their marketing approval to better understand their risk\u2013benefit profiles in real-world settings. As of the 4 January 2023, a total of 69 post-marketing studies concerning the three orphan drugs approved for SMA were identified in clinicaltrials.gov (N = 65; 94.2%) and in the EU PAS register (N = 4; 5.8%). Currently, ongoing studies are primarily aimed at providing evidence concerning the risk\u2013benefit profile of the three drugs in specific populations that were not included in the pivotal trials and to investigate the long-term safety and clinical benefits of these drugs. Real-world data sources collecting information regarding the natural history of the disease and post-marketing surveillance of the available therapies are increasingly becoming essential for generating real-world evidence on this rare disease and its orphan drugs.<\/jats:p>","DOI":"10.3390\/brainsci13101446","type":"journal-article","created":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T02:11:01Z","timestamp":1696990261000},"page":"1446","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Pharmacological Therapies of Spinal Muscular Atrophy: A Narrative Review of Preclinical, Clinical\u2013Experimental, and Real-World Evidence"],"prefix":"10.3390","volume":"13","author":[{"given":"Salvatore","family":"Crisafulli","sequence":"first","affiliation":[{"name":"Department of Medicine, University of Verona, Piazzale Ludovico Antonio Scuro 10, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-8490","authenticated-orcid":false,"given":"Brigida","family":"Boccanegra","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giacomo","family":"Vitturi","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, University of Verona, Piazzale Ludovico Antonio Scuro 10, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1147-7296","authenticated-orcid":false,"given":"Gianluca","family":"Trifir\u00f2","sequence":"additional","affiliation":[{"name":"Department of Diagnostics and Public Health, University of Verona, Piazzale Ludovico Antonio Scuro 10, 37124 Verona, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5652-7341","authenticated-orcid":false,"given":"Annamaria","family":"De Luca","sequence":"additional","affiliation":[{"name":"Department of Pharmacy-Drug Sciences, University of Bari \u201cAldo Moro\u201d, Via E. Orabona 4, 70125 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3233\/JND-190424","article-title":"Advances in Treatment of Spinal Muscular Atrophy\u2014New Phenotypes, New Challenges, New Implications for Care","volume":"7","author":"Schorling","year":"2020","journal-title":"J. Neuromuscul. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1016\/0092-8674(95)90460-3","article-title":"Identification and characterization of a spinal muscular atrophy-determining gene","volume":"80","author":"Lefebvre","year":"1995","journal-title":"Cell"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1016\/j.ncl.2015.07.004","article-title":"Spinal Muscular Atrophy","volume":"33","author":"Kolb","year":"2015","journal-title":"Neurol. 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