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Furthermore, we assess the clinical response to nusinersen treatment in adults with SMA over a longer follow\u2010up period than the previously reported 6\u201314\u2009months.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We included 16 adults with SMA type 3\u20134 for nusinersen treatment over 22\u2009months in this prospective study. We evaluated chitotriosidase\u20101 (CHIT1) and chitinase\u20103\u2010like protein 1 (YKL\u201040) as neuroinflammatory biomarkers in CSF, and neurofilament light chain (NfL) and heavy chain (pNfH) as neurodegenerative markers in CSF and serum at baseline, month 6, 14 and 22, together with a wide range of clinical outcome measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Levels of CHIT1 increased significantly (<jats:italic>p<\/jats:italic>\u2009=\u20090.048) throughout the 22\u2010month treatment period and pNfH decreased significantly (<jats:italic>p<\/jats:italic>\u2009=\u20090.022) in CSF, but both did not correlate with clinical outcome measures. YKL\u201040 correlated strongly with neurofilaments in CSF (rho\u2009=\u20090.76) and decreased significantly (<jats:italic>p<\/jats:italic>\u2009=\u20090.037) in patients with improvements in the revised upper limb module (RULM). Finally, patients showed significant improvements in hand grip strength, hand motor function, medical research council (MRC) sum score, and peak expiratory flow (PEF) after 22\u2009months of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>YKL\u201040 in CSF correlated with clinical improvements during nusinersen treatment. In contrast, CHIT1 and pNfH in CSF changed significantly during treatment but did not correlate with clinical outcomes. Finally, we demonstrated a sustained clinical effect of nusinersen treatment in adults after 22\u2009months.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.51625","type":"journal-article","created":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T07:12:03Z","timestamp":1657782723000},"page":"1241-1251","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Biochemical and clinical biomarkers in adult <scp>SMA<\/scp> 3\u20134 patients treated with nusinersen for 22\u2009months"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1742-1744","authenticated-orcid":false,"given":"Bram","family":"De Wel","sequence":"first","affiliation":[{"name":"Department of Neurology University Hospitals Leuven  Leuven Belgium"},{"name":"Laboratory for Muscle Diseases and Neuropathies, Department of Neurosciences, KU Leuven Leuven Brain Institute (LBI)  Leuven 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