{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T19:37:59Z","timestamp":1793993879086,"version":"4.8.0"},"reference-count":21,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T00:00:00Z","timestamp":1714608000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Biomarkers capable of reflecting disease onset and short- and long-term therapeutic effects in individuals with spinal muscular atrophy (SMA) are still an unmet need and phosphorylated neurofilament heavy chain (pNF-H) holds significant promise.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a longitudinal prospective study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) and plasma of 29 individuals with childhood-onset SMA treated with Nuinersen (SMA type 1: <jats:italic>n<\/jats:italic>\u2009=\u20096, 2: <jats:italic>n<\/jats:italic>\u2009=\u200917, 3: <jats:italic>n<\/jats:italic>\u2009=\u20096). pNF-H levels before and during treatment were compared with the levels of controls (<jats:italic>n<\/jats:italic>\u2009=\u200922), patients with Duchenne muscular dystrophy (<jats:italic>n<\/jats:italic>\u2009=\u200917), myotonic dystrophy type 1 (<jats:italic>n<\/jats:italic>\u2009=\u200911), untreated SMA individuals with chronic type 3 disease (<jats:italic>n<\/jats:italic>\u2009=\u20098), and children with presymptomatic SMA (<jats:italic>n<\/jats:italic>\u2009=\u20093).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>SMA type 1 showed the highest mean CSF pNF-H levels before treatment initiation. All Nusinersen-treated individuals (types 1, 2, and 3) showed significantly elevated mean baseline CSF pNF-H compared to controls, which inversely correlated with age at disease onset, age at first dose, disease duration and the initial CHOP INTEND result (SMA type 1 and 2). During 22\u2009months of treatment, CSF pNF-H levels declined during loading doses, stabilizing at reduced levels from the initial maintenance dose in all individuals. Baseline plasma pNF-H levels in type 1 and 2 SMA were significantly increased compared to other cohorts and decreased notably in type 1 after 2\u2009months of treatment and type 2 after 14\u2009months. Conversely, SMA type 3, characterized by lower baseline pNF-H levels, did not show significant fluctuations in plasma pNF-H levels after 14\u2009months of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our findings suggest that CSF pNF-H levels in untreated SMA individuals are significantly higher than in controls and that monitoring of CSF pNF-H levels may serve as an indicator of rapid short-term treatment response in childhood-onset SMA individuals, irrespective of the subtype of the disease, while also suggesting its potential for assessing long-term suppression of neurodegeneration. Plasma pNF-H may serve as an appropriate outcome measure for disease progression and\/or response to treatment in types 1 and 2 but not in type 3. Presymptomatic infants with SMA may show elevated pNF-H levels, confirming early neuronal degeneration.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1394001","type":"journal-article","created":{"date-parts":[[2024,5,2]],"date-time":"2024-05-02T14:20:17Z","timestamp":1714659617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Phosphorylated neurofilament heavy chain in cerebrospinal fluid and plasma as a Nusinersen treatment response marker in childhood-onset SMA individuals from Serbia"],"prefix":"10.3389","volume":"15","author":[{"given":"Milo\u0161","family":"Brku\u0161anin","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Kosa\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vesna","family":"Brankovi\u0107-Sre\u0107kovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Jovanovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stojan","family":"Peri\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jelena","family":"Karanovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzana","family":"Matija\u0161evi\u0107 Jokovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nemanja","family":"Garai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jovan","family":"Pe\u0161ovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrije","family":"Nikoli\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zorica","family":"Stevi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Goran","family":"Braju\u0161kovi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vedrana","family":"Mili\u0107-Ra\u0161i\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Du\u0161anka","family":"Savi\u0107-Pavi\u0107evi\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,5,2]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1038\/344540a0","article-title":"Genetic mapping of chronic childhood-onset spinal muscular atrophy to chromosome 5q11.2-13.3","volume":"344","author":"Brzustowicz","year":"1990","journal-title":"Nature"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1016\/s0960-8966(06)80015-5","article-title":"International SMA consortium meeting. 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