{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:04:37Z","timestamp":1791212677656,"version":"4.1.0"},"reference-count":60,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T00:00:00Z","timestamp":1754697600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["SFB 1506"],"award-info":[{"award-number":["SFB 1506"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010275","name":"Deutsche Gesellschaft f\u00fcr Muskelkranke","doi-asserted-by":"publisher","award":["Ca2\/1"],"award-info":[{"award-number":["Ca2\/1"]}],"id":[{"id":"10.13039\/501100010275","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>\n                      Tofersen is the first effective and approved therapy for superoxide dismutase\u20091 (\n                      <jats:italic>SOD1<\/jats:italic>\n                      )\u2010associated amyotrophic lateral sclerosis (ALS [SOD1\u2010ALS]). Following treatment with tofersen, neurofilament levels in patients' cerebrospinal fluid (CSF) and serum seem to respond earlier than clinical parameters. This evidence prompted us to hypothesize that this novel treatment could provide an opportunity to identify additional biomarkers responsive to therapy in SOD1\u2010ALS.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We investigated a panel of 120 neural, glial, and inflammatory markers in CSF and serum samples longitudinally collected from a total of 28 SOD1\u2010ALS patients at baseline, and after 3, 6 and 12\u2009months of treatment with tofersen, followed by validation with conventional methodology.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified a set of proteins, including neurofilament light chain, neurofilament heavy chain, amyloid\u2010beta 1\u201340 and amyloid\u2010beta 1\u201342, neuropeptide Y (NPY), and ubiquitin C\u2010terminal hydrolase\u2009L1 (UCHL1), whose CSF levels both differed between SOD1\u2010ALS and the control group, and were responsive to tofersen at 3 and 6\u2009months after treatment initiation. Another group of markers, including the neuropentraxin (NPTX) family members NPTX1, NPTX2 and NPTXR, did not separate untreated SOD1\u2010ALS from controls, but was responsive to tofersen. At 12\u2009months on tofersen the levels of neurofilament light chain, neurofilament heavy chain, NPTX1, NPTX2, and NPTXR remained reduced compared with baseline, and correlated with the clinical response to tofersen. Consistent with increasing CSF pleocytosis and intrathecal immunoglobulin production, inflammatory markers were significantly increased after 12\u2009months of treatment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>Our results highlight a complex, time\u2010dependent differential response of CSF biomarkers to tofersen treatment, and may pave the way for developing a panel of responsive proteins to make biomarker endpoints more robust in clinical trials for SOD1\u2010ALS and beyond. ANN NEUROL 2025;98:1318\u20131334<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.70025","type":"journal-article","created":{"date-parts":[[2025,8,9]],"date-time":"2025-08-09T07:38:48Z","timestamp":1754725128000},"page":"1318-1334","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Targeted Proteomics upon Treatment with Tofersen Identifies Novel Response Markers for Superoxide Dismutase 1\u2010Linked Amyotrophic Lateral Sclerosis"],"prefix":"10.1002","volume":"98","author":[{"given":"Christina","family":"Steffke","sequence":"first","affiliation":[{"name":"Department of Neurology Ulm University  Ulm Germany"},{"name":"Institute of Anatomy and Cell Biology  Ulm Germany"},{"name":"International Graduate School Ulm University  Ulm Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karthik","family":"Baskar","sequence":"additional","affiliation":[{"name":"Institute of Anatomy and Cell 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