{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:34:41Z","timestamp":1787312081984,"version":"build-2736575974"},"reference-count":70,"publisher":"SAGE Publications","issue":"5-6","license":[{"start":{"date-parts":[[2026,2,8]],"date-time":"2026-02-08T00:00:00Z","timestamp":1770508800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Human Gene Therapy"],"published-print":{"date-parts":[[2026,3,1]]},"abstract":"<jats:p>\n                    CLN5 disease, caused by mutations in the\n                    <jats:italic toggle=\"yes\">CLN5<\/jats:italic>\n                    gene, is a form of neuronal ceroid lipofuscinoses (Batten disease). Patients suffer progressive motor dysfunction, vision loss, seizures, and dementia, leading to premature death. Here, we report a preclinical study of AAV9-mediated gene therapy in a\n                    <jats:italic toggle=\"yes\">Cln5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mouse model. Single-dose AAV9 carrying human\n                    <jats:italic toggle=\"yes\">CLN5<\/jats:italic>\n                    driven by the CAG or human synapsin 1 promoter (hSYN) was administered via intracerebroventricular injection into neonatal and juvenile\n                    <jats:italic toggle=\"yes\">Cln5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. Treatment efficacy was evaluated by assessment of neurodegeneration, neuroinflammation, locomotor function, and survival. AAV9 expressing\n                    <jats:italic toggle=\"yes\">CLN5<\/jats:italic>\n                    driven by the hSYN promoter significantly alleviated neurodegeneration, improved biochemical and glycosphingolipid profiles, neuropathological and locomotor function, and extended lifespan of the\n                    <jats:italic toggle=\"yes\">Cln5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice. However, gene transfer employing the CAG promoter demonstrated limited therapeutic efficacy. Furthermore, delayed intervention in juveniles provided superior therapeutic response compared with early neonatal intervention and normalized lifespan. Finally, blood plasma neurofilament light that is significantly elevated in the\n                    <jats:italic toggle=\"yes\">Cln5<\/jats:italic>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice is restored to normal wildtype levels following treatment. These results indicate that brain-directed adeno-associated virus (AAV) gene therapy could be a promising treatment strategy for CLN5 disease and efficacy might be monitored using a noninvasive blood plasma biomarker.\n                  <\/jats:p>","DOI":"10.1177\/10430342251403448","type":"journal-article","created":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T07:41:19Z","timestamp":1766994079000},"page":"241-261","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Brain-Directed AAV Gene Therapy Rescues a Mouse Model of the CLN5 Form of Neuronal Ceroid Lipofuscinosis Disease and Normalizes a Blood Plasma Biomarker of Neurodegeneration"],"prefix":"10.1177","volume":"37","author":[{"given":"Wenfei","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, UCL School of Pharmacy, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy F.","family":"Geard","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UCL School of Pharmacy, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Massaro","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UCL School of Pharmacy, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael P.","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, UCL School of Pharmacy, University College London, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikel","family":"Aristorena","sequence":"additional","affiliation":[{"name":"Centre for Gene Therapy and Regenerative Medicine, King\u2019s College London, Guy\u2019s Hospital, London, United 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Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reuben","family":"Bush","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danielle","family":"te Vruchte","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Priestman","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rhiannon","family":"Laban","sequence":"additional","affiliation":[{"name":"Fluid Biomarker Laboratory and Biomarker Factory, UK Dementia Research Institute at UCL, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Veleva","sequence":"additional","affiliation":[{"name":"Fluid Biomarker Laboratory and Biomarker Factory, UK Dementia Research Institute at UCL, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda J.","family":"Heslegrave","sequence":"additional","affiliation":[{"name":"Fluid Biomarker Laboratory and Biomarker Factory, UK Dementia Research Institute at UCL, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Fluid Biomarker Laboratory and Biomarker Factory, UK Dementia Research Institute at UCL, London, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances M.","family":"Platt","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of Oxford, Oxford, United 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