{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:23:19Z","timestamp":1792887799887,"version":"4.5.0"},"reference-count":69,"publisher":"American Society for Clinical Investigation","issue":"22","license":[{"start":{"date-parts":[[2025,11,17]],"date-time":"2025-11-17T00:00:00Z","timestamp":1763337600000},"content-version":"vor","delay-in-days":62,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"crossref","award":["n\/a"],"award-info":[{"award-number":["n\/a"]}],"id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,17]]},"abstract":"<jats:sec>\n                    <jats:title>BACKGROUND<\/jats:title>\n                    <jats:p>\n                      Spinal muscular atrophy (SMA) is a rare genetic neuromuscular disease caused by deletions or mutations of the survival motor neuron 1 (\n                      <jats:italic>SMN1<\/jats:italic>\n                      ) gene. Despite the availability of genetically based treatments for SMA, functional impairments and weakness persist in treated symptomatic individuals. This study addresses whether additional treatment after gene transfer therapy could provide further clinical benefits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Interim day 302 findings are described from the phase IV open-label RESPOND trial evaluating nusinersen in participants aged \u226436 months who had suboptimal clinical status following onasemnogene abeparvovec (OA) treatment, as determined by the investigator.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      Thirty-seven participants included in the interim analysis were symptomatic at the time of OA administration. Most (92%) had 2\n                      <jats:italic>SMN2<\/jats:italic>\n                      gene copies. Age at first nusinersen dose (median) was 9.1 (range, 3\u201333) months for participants with 2\n                      <jats:italic>SMN2<\/jats:italic>\n                      copies and 34.2 (range, 31\u201336) months for those with 3\n                      <jats:italic>SMN2<\/jats:italic>\n                      copies, while time from OA dose to first nusinersen dose (median) was 6.3 (range, 3\u201331) and 13.3 (range, 10\u201322) months, respectively. Participants had elevated neurofilament light chain (NfL) levels and low compound muscle action potential (CMAP) amplitudes at baseline, suggesting active neurodegeneration and severe denervation at study entry. Improvements from baseline were observed across a range of outcomes on day 302, including motor function (HINE-2 and CHOP-INTEND total score), achievement of independent sitting, NfL levels, CMAP, and investigator- and caregiver-reported outcomes. Mean NfL levels decreased rapidly from baseline to day 183 and remained low on day 302. Mean ulnar and peroneal CMAP amplitudes increased. No safety concerns were identified.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Improvements in clinical and biomarker outcomes support the benefit of nusinersen treatment in infants and children with suboptimal clinical status following OA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION<\/jats:title>\n                    <jats:p>ClinicalTrials.gov NCT04488133; EudraCT 2020-003492-18.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>FUNDING<\/jats:title>\n                    <jats:p>This study was sponsored by Biogen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1172\/jci193956","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T16:00:51Z","timestamp":1758038451000},"source":"Crossref","is-referenced-by-count":10,"title":["Open-label phase IV trial evaluating nusinersen after onasemnogene abeparvovec in children with spinal muscular atrophy"],"prefix":"10.1172","volume":"135","author":[{"given":"Crystal M.","family":"Proud","sequence":"first","affiliation":[{"name":"Neurology and Neuromuscular Medicine, Children\u2019s Hospital of The King\u2019s Daughters, Norfolk, Virginia, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Finkel","sequence":"additional","affiliation":[{"name":"Center for Experimental Neurotherapeutics, Department of Pediatric Medicine, St. Jude Children\u2019s Research Hospital, Memphis, Tennessee, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie A.","family":"Parsons","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s Hospital Colorado, University of Colorado School of Medicine, Aurora, Colorado, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Masson","sequence":"additional","affiliation":[{"name":"Neuroimmunology and Neuromuscular Disease Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milan, Italy."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Brandsema","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy L.","family":"Kuntz","sequence":"additional","affiliation":[{"name":"Division of Neurology, Ann & Robert H. Lurie Children\u2019s Hospital of Chicago, Chicago, Illinois, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Foster","sequence":"additional","affiliation":[{"name":"Biogen, Maidenhead, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjing","family":"Li","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ross","family":"Littauer","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jihee","family":"Sohn","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Fradette","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bora","family":"Youn","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela D.","family":"Paradis","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the RESPOND Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2025,9,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(08)60921-6"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/8.7.1177"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-022-00380-8"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2018.01.003"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000002445"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(16)31408-8"},{"key":"B7"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1710504"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.100862"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27853"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3233\/JND-221667"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.lanepe.2024.101092"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00001-6"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00251-9"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.52093"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27363"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1515"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-021-01483-7"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.210"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(23)00419-2"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1186\/s12887-022-03671-x"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.adg6518"},{"key":"B23","unstructured":"A study to learn about the effect of nusinersen (BIIB058) given as injections to children with spinal muscular atrophy (SMA) who were previously treated with onasemnogene abeparvovec (RESPOND). https:\/\/clinicaltrials.gov NCT04488133. 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Final safety and efficacy data from the SHINE study in participants with infantile-onset and later-onset SMA. Paper presented at: 2024 Annual Cure SMA Research and Clinical Care Meeting; June 5\u20137, 2024; Austin, Texas, USA. 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