{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T20:42:58Z","timestamp":1789764178066,"version":"4.0.1"},"reference-count":63,"publisher":"SAGE Publications","issue":"3","license":[{"start":{"date-parts":[[2013,12,29]],"date-time":"2013-12-29T00:00:00Z","timestamp":1388275200000},"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":[[2014,3]]},"abstract":"<jats:p>\n                    Juvenile neuronal ceroid lipofuscinosis (JNCL or CLN3 disease) is an autosomal recessive lysosomal storage disease resulting from mutations in the\n                    <jats:italic toggle=\"yes\">CLN3<\/jats:italic>\n                    gene that encodes a lysosomal membrane protein. The disease primarily affects the brain with widespread intralysosomal accumulation of autofluorescent material and fibrillary gliosis, as well as the loss of specific neuronal populations. As an experimental treatment for the CNS manifestations of JNCL, we have developed a serotype rh.10 adeno-associated virus vector expressing the human\n                    <jats:italic toggle=\"yes\">CLN3<\/jats:italic>\n                    cDNA (AAVrh.10hCLN3). We hypothesized that administration of AAVrh.10hCLN3 to the\n                    <jats:italic toggle=\"yes\">Cln3<\/jats:italic>\n                    <jats:sup>\u0394ex7\/8<\/jats:sup>\n                    knock-in mouse model of JNCL would reverse the lysosomal storage defect, as well as have a therapeutic effect on gliosis and neuron loss. Newborn\n                    <jats:italic toggle=\"yes\">Cln3<\/jats:italic>\n                    <jats:sup>\u0394ex7\/8<\/jats:sup>\n                    mice were administered 3\u00d710\n                    <jats:sup>10<\/jats:sup>\n                    genome copies of AAVrh.10hCLN3 to the brain, with control groups including untreated\n                    <jats:italic toggle=\"yes\">Cln3<\/jats:italic>\n                    <jats:sup>\u0394ex7\/8<\/jats:sup>\n                    mice and wild-type littermate mice. After 18 months,\n                    <jats:italic toggle=\"yes\">CLN3<\/jats:italic>\n                    transgene expression was detected in various locations throughout the brain, particularly in the hippocampus and deep anterior cortical regions. Changes in the CNS neuronal lysosomal accumulation of storage material were assessed by immunodetection of subunit C of ATP synthase, luxol fast blue staining, and periodic acid-Schiff staining. For all parameters,\n                    <jats:italic toggle=\"yes\">Cln3<\/jats:italic>\n                    <jats:sup>\u0394ex7\/8<\/jats:sup>\n                    mice exhibited abnormal lysosomal accumulation, but AAVrh.10hCLN3 administration resulted in significant reductions in storage material burden. There was also a significant decrease in gliosis in AAVrh.10hCLN3-treated\n                    <jats:italic toggle=\"yes\">Cln3<\/jats:italic>\n                    <jats:sup>\u0394ex7\/8<\/jats:sup>\n                    mice, and a trend toward improved neuron counts, compared with their untreated counterparts. These data demonstrate that AAVrh.10 delivery of a wild-type cDNA to the CNS is not harmful and instead provides a partial correction of the neurological lysosomal storage defect of a disease caused by a lysosomal membrane protein, indicating that this may be an effective therapeutic strategy for JNCL and other diseases in this category.\n                  <\/jats:p>","DOI":"10.1089\/hum.2012.253","type":"journal-article","created":{"date-parts":[[2013,12,30]],"date-time":"2013-12-30T02:45:17Z","timestamp":1388371517000},"page":"223-239","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":42,"title":["Partial Correction of the CNS Lysosomal Storage Defect in a Mouse Model of Juvenile Neuronal Ceroid Lipofuscinosis by Neonatal CNS Administration of an Adeno-Associated Virus Serotype rh.10 Vector Expressing the Human\n                    <i>CLN3<\/i>\n                    Gene"],"prefix":"10.1177","volume":"25","author":[{"given":"Dolan","family":"Sondhi","sequence":"first","affiliation":[{"name":"Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma C.","family":"Scott","sequence":"additional","affiliation":[{"name":"Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvin","family":"Chen","sequence":"additional","affiliation":[{"name":"Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neil R.","family":"Hackett","sequence":"additional","affiliation":[{"name":"Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.S.","family":"Wong","sequence":"additional","affiliation":[{"name":"The Institute of Psychiatry","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka","family":"Kubiak","sequence":"additional","affiliation":[{"name":"The Institute of Psychiatry","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemanth R.","family":"Nelvagal","sequence":"additional","affiliation":[{"name":"The Institute of Psychiatry","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yewande","family":"Pearse","sequence":"additional","affiliation":[{"name":"The Institute of Psychiatry","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan L.","family":"Cotman","sequence":"additional","affiliation":[{"name":"Center for Human Genetic Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan D.","family":"Cooper","sequence":"additional","affiliation":[{"name":"The Institute of Psychiatry","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald G.","family":"Crystal","sequence":"additional","affiliation":[{"name":"Cornell University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2013,12,29]]},"reference":[{"key":"e_1_3_3_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2005.12.004"},{"key":"e_1_3_3_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s002340050427"},{"key":"e_1_3_3_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2004.02.010"},{"key":"e_1_3_3_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr110"},{"key":"e_1_3_3_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-8628(19980526)77:4<289::AID-AJMG8>3.0.CO;2-I"},{"key":"e_1_3_3_7_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M602180200"},{"key":"e_1_3_3_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymthe.2005.11.015"},{"key":"e_1_3_3_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2008.9"},{"key":"e_1_3_3_10_1","unstructured":"ClinicalTrials.gov (2011). AAVRh.10 administered to children with late infantile neuronal ceroid lipofuscinosis with uncommon genotypes or moderate\/severe impairment. 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(1999). CLN3 juvenile NCL. In The Neuronal Ceroid Lipofuscinoses (Batten Disease). Goebel H.H., ed. 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