{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T15:11:30Z","timestamp":1788361890692,"version":"build-2803163510"},"reference-count":35,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T00:00:00Z","timestamp":1564358400000},"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":["J Cereb Blood Flow Metab"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:p>\n                    In Tay-Sachs and Sandhoff disease, a deficiency of the lysosomal enzyme \u03b2-hexosaminidase causes GM2 and other gangliosides to accumulate in neurons and triggers neurodegeneration. Although the pathology centers on neurons, \u03b2-hexosaminidase is mainly expressed outside of neurons, suggesting that gene therapy of these diseases should target non-neuronal cells to reconstitute physiological conditions. Here, we tested in Hexb\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice, a model of Sandhoff disease, to determine whether endothelial expression of the genes for human \u03b2-hexosaminidase subunit A and B ( HEXA, HEXB) is able to reduce disease symptoms and prolong survival of the affected mice. The brain endothelial selective vectors AAV-BR1-CAG- HEXA and AAV-BR1-CAG- HEXB transduced brain endothelial cells, which subsequently released \u03b2-hexosaminidase enzyme. In\u00a0vivo intravenous administration of the gene vectors to adult and neonatal mice prolonged survival. They improved neurological function and reduced accumulation of the ganglioside GM2 and the glycolipid GA2 as well as astrocytic activation. Overall, the data demonstrate that endothelial cells are a suitable target for intravenous gene therapy of GM2 gangliosidoses and possibly other lysosomal storage disorders.\n                  <\/jats:p>","DOI":"10.1177\/0271678x19865917","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T21:44:31Z","timestamp":1564436671000},"page":"1338-1350","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":28,"title":["Brain endothelial specific gene therapy improves experimental Sandhoff disease"],"prefix":"10.1177","volume":"40","author":[{"given":"Godwin","family":"Dogbevia","sequence":"first","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, University of L\u00fcbeck, L\u00fcbeck, Germany"},{"name":"Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Grasshoff","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alaa","family":"Othman","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Penno","sequence":"additional","affiliation":[{"name":"Department of Cell Biology of Lipids, LIMES Institute, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4510-9718","authenticated-orcid":false,"given":"Markus","family":"Schwaninger","sequence":"additional","affiliation":[{"name":"Institute for Experimental and Clinical Pharmacology and Toxicology, University of L\u00fcbeck, L\u00fcbeck, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2019,7,29]]},"reference":[{"key":"bibr1-0271678X19865917","first-page":"9","volume-title":"Fabry disease: Perspectives from 5 years of FOS","author":"Fuller M","year":"2006"},{"key":"bibr2-0271678X19865917","volume-title":"Fabry disease: Perspectives from 5 years of FOS","author":"Neufeld EF","year":"2006"},{"key":"bibr3-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0822-13.2013"},{"key":"bibr4-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1172\/JCI85300"},{"key":"bibr5-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22262"},{"key":"bibr6-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2012.44"},{"key":"bibr7-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/nbt.1515"},{"key":"bibr8-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2014.240"},{"key":"bibr9-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3389"},{"key":"bibr10-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddy012"},{"key":"bibr11-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.10.047"},{"key":"bibr12-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2017.163"},{"key":"bibr13-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2016.109"},{"key":"bibr14-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/ng1095-170"},{"key":"bibr15-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3554"},{"key":"bibr16-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.07.028"},{"key":"bibr17-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1052389"},{"key":"bibr18-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1186\/1742-2094-9-186"},{"key":"bibr19-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2009.12.001"},{"key":"bibr20-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2012.152"},{"key":"bibr21-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2025"},{"key":"bibr22-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1002\/ana.24981"},{"key":"bibr23-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201506078"},{"key":"bibr24-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1016\/S1525-0016(03)00095-9"},{"key":"bibr25-0271678X19865917","doi-asserted-by":"crossref","unstructured":"Xiao X, Li J, Samulski RJ. Production of high-titer recombinant adeno-associated virus vectors in the absence of helper adenovirus.\n                      J Virol\n                      1998; 72: 2224\u20132232.","DOI":"10.1128\/JVI.72.3.2224-2232.1998"},{"key":"bibr26-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20110398"},{"key":"bibr27-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2014.03.014"},{"key":"bibr28-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2016.02.054"},{"key":"bibr29-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1007\/s10719-008-9137-5"},{"key":"bibr30-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt250"},{"key":"bibr31-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0702230104"},{"key":"bibr32-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/mtm.2015.57"},{"key":"bibr33-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/nature25739"},{"key":"bibr34-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14152"},{"key":"bibr35-0271678X19865917","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2017.04.002"}],"container-title":["Journal of Cerebral Blood Flow &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X19865917","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0271678X19865917","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0271678X19865917","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:16:33Z","timestamp":1777493793000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0271678X19865917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,7,29]]},"references-count":35,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2020,6]]}},"alternative-id":["10.1177\/0271678X19865917"],"URL":"https:\/\/doi.org\/10.1177\/0271678x19865917","relation":{},"ISSN":["0271-678X","1559-7016"],"issn-type":[{"value":"0271-678X","type":"print"},{"value":"1559-7016","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,7,29]]}}}