{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T02:13:20Z","timestamp":1783649600017,"version":"3.55.0"},"reference-count":14,"publisher":"Springer Science and Business Media LLC","issue":"2","license":[{"start":{"date-parts":[[2026,2,1]],"date-time":"2026-02-01T00:00:00Z","timestamp":1769904000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T00:00:00Z","timestamp":1770768000000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder. We describe four patients with hereditary ALS caused by the p.Gly94Ser\n                    <jats:italic>SOD1<\/jats:italic>\n                    mutation who were treated monthly with the intrathecal antisense oligonucleotide tofersen in a clinical setting at Landspitali University Hospital of Iceland. After initiating treatment 15\u201326\u00a0months ago, no significant clinical deterioration was observed, and three patients showed signs of clinical improvement, with some recovery of motor function. All four patients currently present with chronic nonprogressive ALS, a phenotype not previously observed or documented. Concomitantly, the concentration of neurofilament light chain (Nf-L) in the cerebrospinal fluid decreased to the normal range. This clinical benefit and decrease in Nf-L levels were detected regardless of the patient\u2019s initial ALSFRS-R score. No serious adverse events were observed. Notably, we observed a clinically meaningful effect in two patients who had been ill for several years before treatment was instituted, raising questions about who should receive treatment and the biology of paresis and motor neuron cell loss in patients with ALS. Although only a minority of ALS patients carry a\n                    <jats:italic>SOD1<\/jats:italic>\n                    mutation, the advent of this new precision medicine has profound implications for ALS management.\n                  <\/jats:p>","DOI":"10.1007\/s00415-025-13579-y","type":"journal-article","created":{"date-parts":[[2026,2,11]],"date-time":"2026-02-11T13:48:45Z","timestamp":1770817725000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Treating SOD1-ALS with tofersen results in nonprogressive chronic ALS\u2014a case series from Iceland"],"prefix":"10.1007","volume":"273","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-0576-5990","authenticated-orcid":false,"given":"Bjorn Logi","family":"Thorarinsson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4507-2935","authenticated-orcid":false,"given":"Olafur Arni","family":"Sveinsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust","family":"Hilmarsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thora Bjorg","family":"Sigurthorsdottir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0094-5429","authenticated-orcid":false,"given":"Peter Munch","family":"Andersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,11]]},"reference":[{"key":"13579_CR1","first-page":"23","volume":"2","author":"JM Charcot","year":"1874","unstructured":"Charcot JM (1874) De la scl\u00e9rose lat\u00e9rale amyotrophique. Prog Med 2:23","journal-title":"Prog Med"},{"key":"13579_CR2","unstructured":"Clinical Genome Resource. ClinGen ALS Gene Curation Expert Panel. 2025. Available from: https:\/\/clinicalgenome.org\/affiliation\/40096\/"},{"issue":"1","key":"13579_CR3","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/S1474-4422(24)00479-4","volume":"24","author":"M Benatar","year":"2025","unstructured":"Benatar M, Robertson J, Andersen PM (2025) Amyotrophic lateral sclerosis caused by SOD1 variants: from genetic discovery to disease prevention. 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N Engl J Med 387(12):1099\u20131110","journal-title":"N Engl J Med"},{"issue":"2","key":"13579_CR6","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1056\/NEJMoa2003715","volume":"383","author":"T Miller","year":"2020","unstructured":"Miller T, Cudkowicz M, Shaw PJ et al (2020) Phase 1\u20132 trial of antisense oligonucleotide tofersen for SOD1 ALS. N Engl J Med 383(2):109\u2013119","journal-title":"N Engl J Med"},{"key":"13579_CR7","unstructured":"U.S. Food and Drug Administration. (2025) FDA approves treatment of amyotrophic lateral sclerosis associated with a mutation in the SOD1 gene. Silver Spring (MD): FDA. Available from: https:\/\/www.fda.gov\/drugs\/news-events-human-drugs\/fda-approves-treatment-amyotrophic-lateral-sclerosis-associated-mutation-sod1-gene"},{"key":"13579_CR8","unstructured":"European Medicines Agency (2025). Qalsody: EPAR summary for the public [Internet]. Amsterdam: EMA. Available from: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/qalsody"},{"key":"13579_CR9","doi-asserted-by":"publisher","DOI":"10.1016\/j.eclinm.2024.102495","volume":"69","author":"M Wiesenfarth","year":"2024","unstructured":"Wiesenfarth M, Dorst J, Brenner D, Elmas Z, Parlak \u00d6, Uzelac Z et al (2024) Effects of tofersen treatment in patients with SOD1-ALS in a real-world setting: a 12-month multicenter cohort study from the German early access program. eClinicalMedicine 69:102495. https:\/\/doi.org\/10.1016\/j.eclinm.2024.102495","journal-title":"eClinicalMedicine"},{"key":"13579_CR10","doi-asserted-by":"publisher","first-page":"5177","DOI":"10.1007\/s00415-024-12437-7","volume":"271","author":"M Sabatelli","year":"2024","unstructured":"Sabatelli M, Cerri F, Zuccarino R, Patanella AK, Bernardo D, Bisogni G et al (2024) Long-term treatment of SOD1 ALS with tofersen: a multicentre experience in 17 patients. 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Since 1993, Director of the ALSgenetic laboratory at Ume\u00e5 University Hospital that performs not-for-profit research genetic testing. Since 2021, member of the ClinGen ALS Gene variant Curation Expert panel. PMA report grants from the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Ulla-Carin Lindquist Foundation, NEURO, the Brain Foundation and the Fort Knox Charity Foundation and the Olsson & Olsson Charity Foundation; as well as consulting fees from Biogen, Avrion, Arrowhead, Regeneron, uniQure, Orphazyme and Roche. None of the other authors has any financial disclosures or conflicts to report.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}],"article-number":"140"}}