{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T02:53:12Z","timestamp":1771296792572,"version":"3.50.1"},"reference-count":63,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T00:00:00Z","timestamp":1674777600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"United Kingdom Medical Research Council","award":["MR\/N019075\/1"],"award-info":[{"award-number":["MR\/N019075\/1"]}]},{"name":"United Kingdom Medical Research Council","award":["MR\/R026084\/1"],"award-info":[{"award-number":["MR\/R026084\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sciences"],"abstract":"<jats:p>The introduction of intracerebroventricular (ICV) enzyme replacement therapy (ERT) for treatment of neuronal ceroid lipofuscinosis type 2 (CLN2) disease has produced dramatic improvements in disease management. However, assessments of therapeutic effect for ICV ERT are limited to clinical observational measures, namely the CLN2 Clinical Rating Scale, a subjective measure of motor and language performance. There is a need for an objective biomarker to enable assessments of disease progression and response to treatment. To address this, we investigated whether the proportion of cells with abnormal storage inclusions on electron microscopic examination of peripheral blood buffy coats could act as a biomarker of disease activity in CLN2 disease. We conducted a prospective longitudinal analysis of six patients receiving ICV ERT. We demonstrated a substantial and continuing reduction in the proportion of abnormal cells over the course of treatment, whereas symptomatic scores revealed little or no change over time. Here, we proposed the use of the proportion of cells with abnormal storage as a biomarker of response to therapy in CLN2. In the future, as more tissue-specific biomarkers are developed, the buffy coats may form part of a panel of biomarkers in order to give a more holistic view of a complex disease.<\/jats:p>","DOI":"10.3390\/brainsci13020209","type":"journal-article","created":{"date-parts":[[2023,1,27]],"date-time":"2023-01-27T03:02:48Z","timestamp":1674788568000},"page":"209","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Buffy Coat Score as a Biomarker of Treatment Response in Neuronal Ceroid Lipofuscinosis Type 2"],"prefix":"10.3390","volume":"13","author":[{"given":"Siyamini","family":"Sivananthan","sequence":"first","affiliation":[{"name":"Department of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Glenn","family":"Anderson","sequence":"additional","affiliation":[{"name":"Department of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UK"},{"name":"Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barbara","family":"Csanyi","sequence":"additional","affiliation":[{"name":"Department of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Children\u2019s Neurosciences, Evelina London Children\u2019s Hospital, London SE1 7EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9712-6122","authenticated-orcid":false,"given":"Paul","family":"Gissen","sequence":"additional","affiliation":[{"name":"Department of Inherited Metabolic Diseases, Great Ormond Street Hospital, London WC1N 1EH, UK"},{"name":"Institute for Health Research Great Ormond Street Hospital Biomedical Research Centre, University College London, London WC1N 1EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,1,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1016\/j.bbadis.2015.05.011","article-title":"Genetics of the Neuronal Ceroid Lipofuscinoses (Batten Disease)","volume":"1852","author":"Mole","year":"2015","journal-title":"Biochim. 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