{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T04:19:23Z","timestamp":1791001163327,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2019,12,8]],"date-time":"2019-12-08T00:00:00Z","timestamp":1575763200000},"content-version":"vor","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008484","name":"BioMarin Pharmaceutical","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008484","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":[[2019,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>Neuronal ceroid lipofuscinosis type 2 (CLN2 disease) is a rare, progressive, fatal neurodegenerative pediatric disorder resulting from deficiencies of the lysosomal enzyme tripeptidyl peptidase 1 that are caused by mutations in <jats:italic>TPP1<\/jats:italic>. Identifying biomarkers of CLN2 disease progression will be important in assessing the efficacy of therapeutic interventions for this disorder. Neurofilament light is an intrinsic component of healthy neurons; elevated circulating extracellular neurofilament light is a biomarker of neuropathology in several adult\u2010onset neurological diseases. Our objective was to assess whether circulating neurofilament light is a biomarker that is responsive to enzyme replacement therapy (ERT) in CLN2 disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Using an ultrasensitive immunoassay, we assessed plasma neurofilament light changes during disease progression in a canine model of CLN2 disease and in ERT clinical trial CLN2 disease patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In tripeptidyl peptidase 1 (<jats:italic>TPP1<\/jats:italic>)\u2010null dogs (<jats:italic>N<\/jats:italic>\u00a0=\u00a011), but not in control dogs [<jats:italic>N<\/jats:italic>\u00a0=\u00a06 (<jats:italic>TPP1<\/jats:italic><jats:sup>+\/\u2212<\/jats:sup>) and <jats:italic>N<\/jats:italic>\u00a0=\u00a027 (WT)], neurofilament light levels increased more than tenfold above initial low baseline levels during disease progression. Before treatment in 21 human subjects with CLN2 disease (age range: 1.72\u20136.85\u00a0years), neurofilament light levels were 48\u2010fold higher (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) than in 7 pediatric controls (age range: 8\u201311\u00a0years). Pretreatment neurofilament light did not significantly correlate with disease severity or age. In CLN2 disease subjects receiving ERT, neurofilament light levels decreased by 50% each year over more than 3\u00a0years of treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Our data indicate that circulating neurofilament light is a treatment\u2010responsive biomarker in CLN2 disease and could contribute to understanding of the pathophysiology of this devastating pediatric disorder.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acn3.50942","type":"journal-article","created":{"date-parts":[[2019,12,9]],"date-time":"2019-12-09T04:30:06Z","timestamp":1575865806000},"page":"2437-2447","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Neurofilament light is a treatment\u2010responsive biomarker in CLN2 disease"],"prefix":"10.1002","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0509-1792","authenticated-orcid":false,"given":"Yuanbin","family":"Ru","sequence":"first","affiliation":[{"name":"Research BioMarin Pharmaceutical Inc. 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Novato California 94949"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guoying K.","family":"Yu","sequence":"additional","affiliation":[{"name":"Research BioMarin Pharmaceutical Inc. Novato California 94949"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nancy","family":"Pryer","sequence":"additional","affiliation":[{"name":"Translational Sciences BioMarin Pharmaceutical Inc. Novato California 94949"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R.","family":"Sinclair","sequence":"additional","affiliation":[{"name":"Pharmacological Sciences BioMarin Pharmaceutical Inc. 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