{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T14:42:51Z","timestamp":1786632171195,"version":"build-2736575974"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,12]],"date-time":"2026-06-12T00:00:00Z","timestamp":1781222400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Muscle and Nerve"],"published-print":{"date-parts":[[2026,9]]},"abstract":"ABSTRACT<\/jats:title>\n \n Introduction\/Aims<\/jats:title>\n \n Tofersen is a gene\u2010targeted therapy for individuals with superoxide dismutase 1 (\n SOD1<\/jats:italic>\n ) (+) amyotrophic lateral sclerosis (ALS). Prior to U.S. Food and Drug Administration (FDA) approval, tofersen was made available through expanded access protocol. This study describes the clinical and operational experience of administering tofersen through expanded access protocols at a single academic medical center in the U.S.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Individuals with symptomatic\n SOD1<\/jats:italic>\n (+) ALS (\u2265\u200918\u2009years), who were ineligible for traditional ALS clinical trials, received tofersen via bedside lumbar punctures at Massachusetts General Hospital. Treatment was provided through single\u2010patient and intermediate\u2010sized expanded access protocols prior to FDA approval. Demographic and clinical characteristics, referral\u2010to\u2010treatment timelines, safety outcomes, and operational costs were collected.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Eleven individuals with\n SOD1<\/jats:italic>\n (+) ALS received monthly intrathecal tofersen over a two\u2010year period (July 2021 to July 2023). Most participants were female, and 81.8% had leg\u2010onset ALS. The mean (SD) referral\u2010to\u2010first dose duration was 36 (22.4) days. A total of 120 doses were administered over a two\u2010year period. Tofersen was safe and well tolerated, with no treatment\u2010related serious adverse events. Operational costs totaled $336,620, supported by philanthropy and insurance. The company provided the drug for free.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n This experience demonstrates the feasibility of implementing a resource\u2010intensive expanded access protocol within an academic medical center using a mixed funding model to facilitate early access to emerging ALS therapies.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/mus.70310","type":"journal-article","created":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T04:36:46Z","timestamp":1781325406000},"page":"692-697","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Optimizing Research Operations and Resource Utilization in\n ALS<\/scp>\n Care: Insights From the Tofersen Antisense Oligonucleotide Expanded Access Protocol"],"prefix":"10.1002","volume":"74","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0155-869X","authenticated-orcid":false,"given":"Alison","family":"Wheeler","sequence":"first","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-8484-3183","authenticated-orcid":false,"given":"Kush","family":"Mehta","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danica","family":"Sanders","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cathy","family":"Chin","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Zivalic","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Carey","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"McCaffrey","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pravin","family":"Pant","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carl","family":"Lewenhaupt","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1689-6642","authenticated-orcid":false,"given":"Sarah","family":"Luppino","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel","family":"Jacobs","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shea","family":"Golden","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan","family":"Gifford","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9427-1452","authenticated-orcid":false,"given":"Erica","family":"Scirocco","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mackenzie","family":"Keegan","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munaf","family":"Hatem","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taravat","family":"Yazdanian","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanem P.","family":"Uysal","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Susco","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Centers Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shauna","family":"Schwartzman","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Centers Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen","family":"Branch","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Centers Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9179-283X","authenticated-orcid":false,"given":"Kathryn E.","family":"Hall","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Centers Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanna","family":"Barnas","sequence":"additional","affiliation":[{"name":"Clinical Trials Pharmacy Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Lam","sequence":"additional","affiliation":[{"name":"Clinical Trials Pharmacy Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hagar","sequence":"additional","affiliation":[{"name":"Neurological Clinical Research Institute Grants Administration Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol Ann","family":"Hannan","sequence":"additional","affiliation":[{"name":"Neurological Clinical Research Institute Grants Administration Massachusetts General Hospital Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0505-1168","authenticated-orcid":false,"given":"Sabrina","family":"Paganoni","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James D.","family":"Berry","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3350-338X","authenticated-orcid":false,"given":"Mark","family":"Garret","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Scalia","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2648-7625","authenticated-orcid":false,"given":"Suma","family":"Babu","sequence":"additional","affiliation":[{"name":"Sean M. Healey and AMG Center for ALS and the Neurological Clinical Research Institute Massachusetts General Hospital, Harvard Medical School Boston Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,12]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(21)00465-8"},{"issue":"6","key":"e_1_2_11_3_1","first-page":"22","article-title":"Rise of the Genomic Medicine Era in Amyotrophic Lateral Sclerosis","volume":"22","author":"Garret M.","year":"2023","journal-title":"Practical Neurology"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2204705"},{"key":"e_1_2_11_5_1","volume-title":"StatPearls","author":"Cerillo J. 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U.S. Food and Drug Administration \u201dPublished 2024 https:\/\/www.fda.gov\/industry\/medical\u2010products\u2010rare\u2010diseases\u2010and\u2010conditions\/accelerating\u2010access\u2010critical\u2010therapies\u2010als\u2010act\u2010act\u2010als."},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mus.27672"}],"container-title":["Muscle & Nerve"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70310","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/mus.70310","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mus.70310","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T13:52:28Z","timestamp":1786629148000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mus.70310"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,12]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/mus.70310"],"URL":"https:\/\/doi.org\/10.1002\/mus.70310","archive":["Portico"],"relation":{},"ISSN":["0148-639X","1097-4598"],"issn-type":[{"value":"0148-639X","type":"print"},{"value":"1097-4598","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,12]]},"assertion":[{"value":"2026-02-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}