{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:06:31Z","timestamp":1790175991651,"version":"4.1.0"},"reference-count":93,"publisher":"Cambridge University Press (CUP)","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"unspecified","delay-in-days":265,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Expert Rev. Mol. Med."],"published-print":{"date-parts":[[2026]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec id=\"S1462399426100726_sec1\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Spinal Muscular Atrophy (SMA) is caused by a deficiency of the survival motor neuron (SMN) protein due to loss of\n                      <jats:italic>SMN1<\/jats:italic>\n                      and inefficient compensation by\n                      <jats:italic>SMN2.<\/jats:italic>\n                      This genetic architecture has driven the development of precision therapeutics. Over the past decade, SMA management has progressed from supportive care to RNA-based splicing modulation and gene replacement therapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S1462399426100726_sec2\" sec-type=\"methods\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This review analyzes the evolution of three therapeutic waves in SMA management: antisense oligonucleotides (nusinersen) for\n                      <jats:italic>SMN2<\/jats:italic>\n                      splicing correction; systemic small-molecule splicing modifiers (risdiplam) addressing SMA as a multisystem disorder; and gene replacement therapy (onasemnogene abeparvovec), including recent intrathecal formulations expanding patient eligibility.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S1462399426100726_sec3\" sec-type=\"results\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Precision therapies have profoundly altered the disease trajectory, especially when administered presymptomatically. Nusinersen sustains splicing correction, risdiplam restores SMN across central and peripheral tissues, and gene replacement offers durable, one-time genetic correction. However, critical challenges persist regarding therapeutic durability, optimal treatment sequencing, systemic involvement, and long-term safety.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"S1462399426100726_sec4\" sec-type=\"conclusions\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The evolution of SMA therapies has transformed neurogenetics. Clinical benchmarks have successfully shifted from reactive, symptomatic management to proactive, molecularly targeted precision medicine.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1017\/erm.2026.10072","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:21:48Z","timestamp":1790173308000},"update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":0,"title":["Spinal muscular atrophy as a blueprint for precision therapy in neuromuscular disease"],"prefix":"10.1017","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9644-7610","authenticated-orcid":false,"given":"Busra","family":"Cetin","sequence":"first","affiliation":[{"name":"Akdeniz University Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3471-7073","authenticated-orcid":false,"given":"Melike","family":"Aliciaslan","sequence":"additional","affiliation":[{"name":"Akdeniz University Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3299-5911","authenticated-orcid":false,"given":"Ezgi","family":"Erbasan","sequence":"additional","affiliation":[{"name":"Akdeniz University Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1644-7061","authenticated-orcid":false,"given":"Busra","family":"Cesur Ergun","sequence":"additional","affiliation":[{"name":"Akdeniz University Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8379-5678","authenticated-orcid":false,"given":"Salih","family":"Sanlioglu","sequence":"additional","affiliation":[{"name":"Akdeniz University Faculty of Medicine"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"S1462399426100726_r14","doi-asserted-by":"publisher","DOI":"10.1016\/S0929-693X(20)30270-0"},{"key":"S1462399426100726_r3","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6307"},{"key":"S1462399426100726_r35","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51562"},{"key":"S1462399426100726_r22","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.26.4.1333-1346.2006"},{"key":"S1462399426100726_r2","doi-asserted-by":"publisher","DOI":"10.2741\/3670"},{"key":"S1462399426100726_r46","doi-asserted-by":"publisher","DOI":"10.1038\/ng1207"},{"key":"S1462399426100726_r17","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1515"},{"key":"S1462399426100726_r59","doi-asserted-by":"publisher","DOI":"10.2174\/1566523013348788"},{"key":"S1462399426100726_r66","unstructured":"66. Ebert, M (2025) FDA Approves First Gene Replacement Therapy (Itvisma) for Patients 2 Years and Older with Spinal Muscular atrophy Contemporary Pediatrics. [cited 2026 Feb 2]; Available at https:\/\/www.contemporarypediatrics.com\/view\/fda-approves-first-gene-replacement-therapy-itvisma-for-patients-2-years-and-older-with-spinal-muscular-atrophy?"},{"key":"S1462399426100726_r60","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2004.03.002"},{"key":"S1462399426100726_r7","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcn.2013.04.005"},{"key":"S1462399426100726_r40","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkag484"},{"key":"S1462399426100726_r67","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-025-04119-2"},{"key":"S1462399426100726_r56","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.96.15_supplement.4281"},{"key":"S1462399426100726_r79","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2016.160"},{"key":"S1462399426100726_r23","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1941310"},{"key":"S1462399426100726_r48","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddm379"},{"key":"S1462399426100726_r52","doi-asserted-by":"publisher","DOI":"10.3233\/JND-230197"},{"key":"S1462399426100726_r25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1702752"},{"key":"S1462399426100726_r63","doi-asserted-by":"publisher","DOI":"10.3233\/JND-190403"},{"key":"S1462399426100726_r76","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(25)00225-X"},{"key":"S1462399426100726_r77","unstructured":"77. NMD Pharma.(2023) NMD Pharma Initiates Phase II Trial of NMD670 in Spinal Muscular Atrophy. 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Ionis Pharmaceuticals Inc.(2025) Ionis Announces Biogen to Advance Salanersen into SMA Registrational Studies Based on Positive Interim Phase 1 Results. 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Roche.(2024) Five-Year Data for Roche\u2019s Evrysdi Show the Majority of Treated Children with a Severe form of Spinal Muscular Atrophy (SMA) Achieved or Maintained the Ability to Sit, Stand or Walk. 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