{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T12:45:09Z","timestamp":1785415509207,"version":"3.56.0"},"reference-count":55,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AriSLA\u2014Fondazione Italiana di ricerca per la SLA"},{"name":"Giovanni Marazzina Foundation"},{"DOI":"10.13039\/501100003196","name":"Ministero Della Salute","doi-asserted-by":"crossref","award":["RF-2021-12373036"],"award-info":[{"award-number":["RF-2021-12373036"]}],"id":[{"id":"10.13039\/501100003196","id-type":"DOI","asserted-by":"crossref"}]},{"award":["RF-2021-12373036"],"award-info":[{"award-number":["RF-2021-12373036"]}],"id":[{"id":"https:\/\/ror.org\/00789fa95","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007386","name":"Fondazione Cassa di Risparmio di Modena","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007386","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/03cen5169","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tofersen is a gene-targeted therapy for superoxide dismutase 1 (SOD1)-associated amyotrophic lateral sclerosis (ALS), but neurofilament light chain (NfL) may not fully capture the biological response to treatment. We performed a multicentre retrospective longitudinal study including 24 patients with SOD1-ALS treated with intrathecal tofersen at four Italian referral centres between 2022 and 2025. Cerebrospinal fluid (CSF) and serum biomarkers were assessed at baseline, month 3, month 6, and last available administration using single-molecule array assays to quantify NfL, glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCHL\u20131), and total Tau. NfL decreased after treatment initiation in both CSF and serum, providing the clearest pharmacodynamic signal. In contrast, CSF GFAP increased progressively over follow-up, while CSF total Tau and UCHL\u20131 rose mainly at later timepoints; serum GFAP, total Tau, and UCHL\u20131 also showed increases during follow-up. ALS Functional Rating Scale\u2013Revised trajectories were broadly stable, whereas disease progression rate was lower at last follow-up than at baseline. Greater reductions in CSF NfL were observed in pathogenic versus uncertain SOD1 variants, and early serum NfL and UCHL\u20131 changes were associated with longer-term changes in disease progression. These findings suggest that longitudinal multi-analyte profiling may refine biological response stratification beyond NfL alone in tofersen-treated SOD1-ALS.<\/jats:p>","DOI":"10.3390\/ijms27104208","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T07:49:09Z","timestamp":1778572149000},"page":"4208","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Longitudinal CSF and Serum Biomarker Dynamics in Tofersen-Treated SOD1-ALS: A Real-World Multicentre Cohort Study"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3676-7911","authenticated-orcid":false,"given":"Andrea","family":"Giordano","sequence":"first","affiliation":[{"name":"Neurology 3\u2014Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine, Universit\u00e0 degli Studi di Milano, Via Vanvitelli 32, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9244-9782","authenticated-orcid":false,"given":"Jessica","family":"Mandrioli","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Ospedale Civile Baggiovara, Azienda Ospedaliero Universitaria di Modena, Via Giardini 1355, 41126 Modena, Italy"},{"name":"Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Via Campi 287, 41125 Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1619-2019","authenticated-orcid":false,"given":"Federica","family":"Cerri","sequence":"additional","affiliation":[{"name":"NEuroMuscular Omnicentre, Fondazione Serena ETS, Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Lunetta","sequence":"additional","affiliation":[{"name":"Neurorehabilitation Department, Istituti Clinici Scientifici Maugeri IRCCS, Via Camaldoli 64, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hamidreza","family":"Saebfar","sequence":"additional","affiliation":[{"name":"Neurology 3\u2014Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0370-1905","authenticated-orcid":false,"given":"Marcella","family":"Catania","sequence":"additional","affiliation":[{"name":"Neurology 8\u2014Dementias and Degenerative Diseases of Central Nervous System Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, 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Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7005-689X","authenticated-orcid":false,"given":"Maria","family":"Vizziello","sequence":"additional","affiliation":[{"name":"Neurology 3\u2014Neuroalgology Unit, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria 11, 20133 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Gerardi","sequence":"additional","affiliation":[{"name":"NEuroMuscular Omnicentre, Fondazione Serena ETS, Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8956-7406","authenticated-orcid":false,"given":"Matteo","family":"Far\u00e8","sequence":"additional","affiliation":[{"name":"NEuroMuscular Omnicentre, Fondazione Serena ETS, Piazza dell\u2019Ospedale Maggiore, 3, 20162 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8295-6847","authenticated-orcid":false,"given":"Aida","family":"Zulueta","sequence":"additional","affiliation":[{"name":"Neurorehabilitation Department, Istituti Clinici Scientifici Maugeri IRCCS, Via Camaldoli 64, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8095-1014","authenticated-orcid":false,"given":"Rachele","family":"Piras","sequence":"additional","affiliation":[{"name":"Neurorehabilitation Department, Istituti Clinici Scientifici Maugeri IRCCS, Via Camaldoli 64, 20138 Milan, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matteo","family":"Giacchino","sequence":"additional","affiliation":[{"name":"Department of Neurosciences, Ospedale Civile Baggiovara, Azienda Ospedaliero Universitaria di Modena, Via Giardini 1355, 41126 Modena, Italy"},{"name":"Department of Biomedical, Metabolic and 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