{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T01:40:25Z","timestamp":1790991625961,"version":"4.1.0"},"reference-count":24,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2023,6,26]],"date-time":"2023-06-26T00:00:00Z","timestamp":1687737600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2023,9,8]]},"abstract":"<jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Pharmacokinetic\/pharmacodynamic modeling indicates that the higher dose of nusinersen\n            may be associated with a clinically meaningful increase in efficacy above that seen with\n            the 12-mg approved dose.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>Here we describe both the design of DEVOTE (NCT04089566), a 3-part clinical study\n            evaluating safety, tolerability, and efficacy of higher dose of nusinersen, and results\n            from the initial Part A.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>DEVOTE Part A evaluates safety and tolerability of a higher nusinersen dose; Part B\n            assesses efficacy in a randomized, double-blind design; and Part C assesses safety and\n            tolerability of participants transitioning from the 12-mg dose to higher doses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>In the completed Part A of DEVOTE, all 6 enrolled participants aged 6.1\u201312.6 years have\n            completed the study. Four participants experienced treatment-emergent adverse events\n            (TEAEs), the majority of which were mild. Common TEAEs of headache, pain, chills,\n            vomiting, and paresthesia were considered related to the lumbar puncture procedure.\n            There were no safety concerns regarding clinical or laboratory parameters. Nusinersen\n            levels in the cerebrospinal fluid were within the range of modeled predictions for\n            higher dose of nusinersen. While Part A was not designed for assessing efficacy, most\n            participants showed stabilization or improvement in motor function. Parts B and C of\n            DEVOTE are ongoing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec specific-use=\"heading-level-1\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>The findings from Part A of the DEVOTE study support further development of higher dose\n            of nusinersen.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3233\/jnd-221667","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T03:38:59Z","timestamp":1748403539000},"page":"813-823","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":19,"title":["DEVOTE Study Exploring Higher Dose of Nusinersen in Spinal Muscular Atrophy:          Study Design and Part A Results"],"prefix":"10.1177","volume":"10","author":[{"given":"Richard S.","family":"Finkel","sequence":"first","affiliation":[{"name":"Center for Experimental Neurotherapeutics","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John W.","family":"Day","sequence":"additional","affiliation":[{"name":"Stanford University School of Medicine","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel Ignacio","family":"Pascual Pascual","sequence":"additional","affiliation":[{"name":"Hospital Universitario La Paz","place":["Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique M.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Royal Children\u2019s Hospital,\r          Parkville, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Catholic University","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl C.","family":"De Vivo","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Montes","sequence":"additional","affiliation":[{"name":"Columbia University Irving Medical Center","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juliana","family":"Gurgel-Giannetti","sequence":"additional","affiliation":[{"name":"Universidade Federal de Minas Gerais","place":["Brazil"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Monine","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Gambino","sequence":"additional","affiliation":[{"name":"Biogen, Maidenhead, Berkshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Makepeace","sequence":"additional","affiliation":[{"name":"Biogen, Maidenhead, Berkshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Foster","sequence":"additional","affiliation":[{"name":"Biogen, Maidenhead, Berkshire, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenek","family":"Berger","sequence":"additional","affiliation":[{"name":"Biogen, Cambridge, MA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the DEVOTE Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2023,6,26]]},"reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-022-00380-8"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2017.52"},{"key":"e_1_3_5_4_2","unstructured":"DarrasBT MonaniUR De VivoDC. Genetic disorders affecting the motor neuron: Spinal muscular atrophy. In: Swaiman KF Ashwal S Ferriero DM Schor NF Finkel RS Gropman AL et al. editors. Swaiman\u2019s Pediatric Neurology: Principles snd Practice 6th ed. Edinburgh: Elsevier; 2017. pp. 1057-64."},{"key":"e_1_3_5_5_2","unstructured":"SPINRAZA (nusinersen) injection for intrathecal use. Prescribing Information. Cambridge MA: Biogen; 2016 [updated 2023 February; cited 2023 April 19]. Available from: www.spinraza.com\/content\/dam\/commercial\/specialty\/spinraza\/caregiver\/en_us\/pdf\/spinraza-prescribing-information.pdf."},{"key":"e_1_3_5_6_2","unstructured":"SPINRAZA (nusinersen). Summary of Product Characteristics. The Netherlands: Biogen; 2017 [updated 2022 February 02; cited 2023 April 19]. Available from: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/spinraza-epar-product-information_en.pdf"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3001777"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1941310"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1702752"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1710504"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007527"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2019.09.007"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(20)30037-5"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpn.2020.05.002"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.3233\/JND-190416"},{"key":"e_1_3_5_16_2","unstructured":"DarrasBT ChiribogaCA FarrarMA MercuriE KirschnerJ KuntzNL et al. Longer-term treatment with nusinersen: Results in later-onset spinal muscular atrophy from the SHINE study. Cure SMA - 2020 Annual Conference (Virtual Presentation). June 11-14 2020."},{"key":"e_1_3_5_17_2","unstructured":"KirschnerJ CrawfordTO RyanMM FinkelRS SwobodaKJ De VivoDC et al. Nusinersen Effect in presymptomatic SMA infants: 4.9 year interim of the NURTURE study. SMA Europe - 3rd International Scientific Congress on Spinal Muscular Atrophy. October 21-23 2022; Barcelona Spain."},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27187"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-4642(21)00100-0"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/acn3.51562"},{"key":"e_1_3_5_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2007.05.009"},{"key":"e_1_3_5_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/mus.25430"},{"key":"e_1_3_5_23_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2006.tb02379.x"},{"key":"e_1_3_5_24_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2021.02.014"},{"key":"e_1_3_5_25_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40263-019-00656-w"}],"container-title":["Journal of Neuromuscular Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JND-221667","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.3233\/JND-221667","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.3233\/JND-221667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,27]],"date-time":"2026-01-27T11:44:17Z","timestamp":1769514257000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.3233\/JND-221667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,26]]},"references-count":24,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,9,8]]}},"alternative-id":["10.3233\/JND-221667"],"URL":"https:\/\/doi.org\/10.3233\/jnd-221667","relation":{},"ISSN":["2214-3599","2214-3602"],"issn-type":[{"value":"2214-3599","type":"print"},{"value":"2214-3602","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,26]]}}}