{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T02:23:01Z","timestamp":1793499781733,"version":"4.5.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"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>This study assessed the real-world effectiveness and safety of the enzyme replacement therapy (ERT), cerliponase alfa, to treat neuronal ceroid lipofuscinosis type 2 (CLN2) disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data from the DEM-CHILD database were analyzed, comparing patients who initiated ERT outside clinical trials with natural history (NH) controls. Treated patients were matched 1:1 with NH controls on baseline age and combined motor-language (ML) score on the CLN2 clinical rating scale. Rate of ML score decline, time to unreversed 2-point decline or score of 0, and time to unreversed score of 0 were assessed. Safety was assessed in treated patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty-four ERT-treated patients were eligible (mean [SD] follow-up: 106.7 [64.1] weeks); 21 matched to a NH control, with baseline mean (SD) age of 4.7 (1.9) years and mean (SD) ML score of 3.9 (1.6) points. ERT-treated patients had reduced likelihood of an unreversed ML 2-point decline or score of 0 (HR 0.08; 95% CI 0.02, 0.28; <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.0001), and unreversed ML score of 0 (HR 0.07; 95% CI 0.01, 0.40; <jats:italic>p<\/jats:italic>\u202f=\u202f0.003) versus NH controls. Mean (SD) rate of ML score decline was 0.46 (0.43) versus 1.88 (1.45) points\/48\u202fweeks for ERT-treated and NH groups, respectively (mean difference: 1.42; 95% CI 0.74, 2.10; <jats:italic>p<\/jats:italic>\u202f=\u202f0.0003). Sixteen patients (67%) had treatment-related adverse events; the most common were pyrexia (50%), vomiting (33%), and nausea (21%). No ERT-treated patients died.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Cerliponase alfa for real-world CLN2 disease treatment slowed decline in motor and language function and demonstrated an acceptable safety profile.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1516026","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:36:32Z","timestamp":1741959392000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":15,"title":["Real-world clinical outcomes of patients with CLN2 disease treated with cerliponase alfa"],"prefix":"10.3389","volume":"16","author":[{"given":"Angela","family":"Schulz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schwering","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Wibbeler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena Marie","family":"Westermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luca","family":"Hagenah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Lezius","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashok","family":"Jha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Hunt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Slasor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Reisewitz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Nickel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1093\/med\/9780199590018.003.0007","article-title":"CLN2","volume-title":"The neuronal ceroid lipofuscinoses (Batten disease)","author":"Chang","year":"2011"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1801","DOI":"10.1016\/j.bbadis.2013.04.008","article-title":"NCL diseases - clinical perspectives","volume":"1832","author":"Schulz","year":"2013","journal-title":"Biochim Biophys Acta"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.1016\/j.bbadis.2015.05.007","article-title":"Human NCL neuropathology","volume":"1852","author":"Radke","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1002\/humu.23860","article-title":"Mutation update: review of TPP1 gene variants associated with neuronal ceroid lipofuscinosis CLN2 disease","volume":"40","author":"Gardner","year":"2019","journal-title":"Hum Mutat"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/S2352-4642(18)30179-2","article-title":"Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study","volume":"2","author":"Nickel","year":"2018","journal-title":"Lancet Child Adolesc Health"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"785841","DOI":"10.3389\/fneur.2022.785841","article-title":"Natural history studies in NCL and their expanding role in drug development: experiences from CLN2 disease and relevance for clinical trials","volume":"13","author":"Nickel","year":"2022","journal-title":"Front Neurol"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"e68","DOI":"10.1111\/epi.17269","article-title":"Value of genetic testing for pediatric epilepsy: driving earlier diagnosis of ceroid lipofuscinosis type 2 Batten disease","volume":"63","author":"Leal-Pardinas","year":"2022","journal-title":"Epilepsia"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1186\/s13023-021-01813-5","article-title":"Guidelines on the diagnosis, clinical assessments, treatment and management for CLN2 disease patients","volume":"16","author":"Mole","year":"2021","journal-title":"Orphanet J Rare Dis"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1016\/j.pediatrneurol.2017.01.034","article-title":"Management strategies for CLN2 disease","volume":"69","author":"Williams","year":"2017","journal-title":"Pediatr Neurol"},{"key":"ref10","year":"2024"},{"key":"ref11","year":"2023"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1898","DOI":"10.1056\/NEJMoa1712649","article-title":"Study of intraventricular cerliponase alfa for CLN2 disease","volume":"378","author":"Schulz","year":"2018","journal-title":"N Engl J Med"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1016\/S1474-4422(23)00384-8","article-title":"Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study","volume":"23","author":"Schulz","year":"2024","journal-title":"Lancet Neurol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"232640981878838","DOI":"10.1177\/2326409818788382","article-title":"An adapted clinical measurement tool for the key symptoms of CLN2 disease","volume":"6","author":"Wyrwich","year":"2018","journal-title":"J Inborn Errors Metabol Screen"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1002\/ajmg.10660","article-title":"Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations","volume":"112","author":"Steinfeld","year":"2002","journal-title":"Am J Med Genet"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1111\/j.1750-3639.2004.tb00500.x","article-title":"The genetic spectrum of human neuronal ceroid-lipofuscinoses","volume":"14","author":"Mole","year":"2006","journal-title":"Brain Pathol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1177\/0883073821989154","article-title":"Development of the \"Hamburg best practice guidelines for ICV-enzyme replacement therapy (ERT) in CLN2 disease\" based on 6 years treatment experience in 48 patients","volume":"36","author":"Schwering","year":"2021","journal-title":"J Child Neurol"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1590\/2326-4594-JIEMS-2019-0013","article-title":"The challenges of living with and caring for a child or children affected by neuronal ceroid lipofuscinosis type 2 disease: in-depth family surveys in the United Kingdom and Germany","author":"Schulz","year":"2020","journal-title":"J Inborn Errors Metabol Screen"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"115","DOI":"10.3171\/2021.7.PEDS21129","article-title":"A survival analysis of ventricular access devices for delivery of cerliponase alfa","volume":"29","author":"Craven","year":"2022","journal-title":"J Neurosurg Pediatr"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1516026\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T13:36:35Z","timestamp":1741959395000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1516026\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":19,"alternative-id":["10.3389\/fneur.2025.1516026"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1516026","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,14]]},"article-number":"1516026"}}