{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T21:49:14Z","timestamp":1792273754691,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,4,17]],"date-time":"2019-04-17T00:00:00Z","timestamp":1555459200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005614","name":"Biogen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005614","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2019,5]]},"abstract":"Abstract<\/jats:title>\n \n Objective<\/jats:title>\n \n To evaluate plasma phosphorylated neurofilament heavy chain (\n pNF<\/jats:styled-content>\n \u2010H) as a biomarker in spinal muscular atrophy (\n SMA<\/jats:styled-content>\n ).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Levels of\n pNF<\/jats:styled-content>\n \u2010H were measured using the ProteinSimple\n \u00ae<\/jats:sup>\n platform in plasma samples from infants with\n SMA<\/jats:styled-content>\n enrolled in\n ENDEAR<\/jats:styled-content>\n (\n NCT<\/jats:styled-content>\n 02193074) and infants\/children without neurological disease.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Median\n pNF<\/jats:styled-content>\n \u2010H plasma level was 167.0\u00a0pg\/mL (7.46\u20137,030; n\u00a0=\u00a034) in children without\n SMA<\/jats:styled-content>\n (aged 7\u00a0weeks\u201318\u00a0years) and was higher in those aged\u00a0<\u00a01 versus 1\u201318\u00a0years (\n P\u00a0=\u00a0<\/jats:italic>\n 0.0002). In\n ENDEAR<\/jats:styled-content>\n participants with infantile\u2010onset\n SMA<\/jats:styled-content>\n , median baseline\n pNF<\/jats:styled-content>\n \u2010H level (15,400\u00a0pg\/mL; 2390\u201350,100;\n n<\/jats:italic>\n \u00a0=\u00a0117) was ~10\u2010fold higher than that of age\u2010matched infants without\n SMA<\/jats:styled-content>\n (\n P\u00a0<\/jats:italic>\n <\n \u00a0<\/jats:italic>\n 0.0001) and ~90\u2010fold higher than children without\n SMA<\/jats:styled-content>\n (\n P\u00a0<\/jats:italic>\n <\n \u00a0<\/jats:italic>\n 0.0001). Higher pretreatment\n pNF<\/jats:styled-content>\n \u2010H levels in infants with\n SMA<\/jats:styled-content>\n were associated with younger age at symptom onset, diagnosis, and first dose; lower baseline Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders score; and lower peroneal compound muscle potential amplitude. Nusinersen treatment was associated with a rapid and greater decline in\n pNF<\/jats:styled-content>\n \u2010H levels: nusinersen\u2010treated infants experienced a steep 71.9% decline at 2\u00a0months to 90.1% decline at 10\u00a0months; sham control\u2013treated infants declined steadily by 16.2% at 2\u00a0months and 60.3% at 10\u00a0months.\n <\/jats:p>\n <\/jats:sec>\n \n Interpretation<\/jats:title>\n \n Plasma\n pNF<\/jats:styled-content>\n \u2010H levels are elevated in infants with\n SMA<\/jats:styled-content>\n . Levels inversely correlate with age at first dose and several markers of disease severity. Nusinersen treatment is associated with a significant decline in\n pNF<\/jats:styled-content>\n \u2010H levels followed by relative stabilization. Together these data suggest plasma\n pNF<\/jats:styled-content>\n \u2010H is a promising marker of disease activity\/treatment response in infants with SMA.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/acn3.779","type":"journal-article","created":{"date-parts":[[2019,4,18]],"date-time":"2019-04-18T00:10:02Z","timestamp":1555546202000},"page":"932-944","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":206,"title":["Neurofilament as a potential biomarker for spinal muscular atrophy"],"prefix":"10.1002","volume":"6","author":[{"given":"Basil T.","family":"Darras","sequence":"first","affiliation":[{"name":"Department of Neurology Boston Children's Hospital and Harvard Medical School Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas O.","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Department of Pediatrics Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard S.","family":"Finkel","sequence":"additional","affiliation":[{"name":"Division of Neurology Department of Pediatrics Nemours Children's Hospital Orlando Florida"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugenio","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Catholic University Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Darryl C.","family":"De Vivo","sequence":"additional","affiliation":[{"name":"Departments of Neurology and Pediatrics Columbia University Irving Medical Center New York New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Oskoui","sequence":"additional","affiliation":[{"name":"Department of Neurology and Neurosurgery and Department of Pediatrics McGill University Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo F.","family":"Tizzano","sequence":"additional","affiliation":[{"name":"Department of Clinical and Molecular Genetics and Rare Diseases Unit Hospital Vall d\u2032Hebron and Centro de Investigac\u00edon Biom\u00e9dica en Red Enfermedades Raras (CIBERER) Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monique M.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Royal Children's Hospital Murdoch Children's Research Institute and University of Melbourne Melbourne Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesco","family":"Muntoni","sequence":"additional","affiliation":[{"name":"Dubowitz Neuromuscular Centre University College London London United Kingdom"},{"name":"NIHR Great Ormond Street Hospital Biomedical Research Centre London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guolin","family":"Zhao","sequence":"additional","affiliation":[{"name":"Biogen Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Staropoli","sequence":"additional","affiliation":[{"name":"Biogen Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"McCampbell","sequence":"additional","affiliation":[{"name":"Biogen Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Petrillo","sequence":"additional","affiliation":[{"name":"Biogen Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Stebbins","sequence":"additional","affiliation":[{"name":"Biogen Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Fradette","sequence":"additional","affiliation":[{"name":"Biogen Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wildon","family":"Farwell","sequence":"additional","affiliation":[{"name":"Biogen Cambridge Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte J.","family":"Sumner","sequence":"additional","affiliation":[{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland"},{"name":"Department of Neuroscience Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,4,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-12-417044-5.00008-1"},{"key":"e_1_2_8_3_1","unstructured":"Spinraza 12\u00a0mg solution for injection [summary of product characteristics].http:\/\/www.ema.europa.eu\/docs\/en_GB\/document_library\/EPAR_-_Product_Information\/human\/004312\/WC500229704.pdf. 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