{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T04:42:44Z","timestamp":1789188164872,"version":"build-2803163510"},"reference-count":51,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2016,5,19]],"date-time":"2016-05-19T00:00:00Z","timestamp":1463616000000},"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":[[2016,7]]},"abstract":"<jats:p>\n                    G\n                    <jats:sub>M2<\/jats:sub>\n                    gangliosidosis is a group of neurodegenerative diseases caused by \u03b2-hexosaminidase A (HexA) enzyme deficiency. There is currently no cure. HexA is composed of two similar, nonidentical subunits, \u03b1 and \u03b2, which must interact with the G\n                    <jats:sub>M2<\/jats:sub>\n                    activator protein (GM2AP), a substrate-specific cofactor, to hydrolyze G\n                    <jats:sub>M2<\/jats:sub>\n                    ganglioside. Mutations in either subunit or the activator can result in the accumulation of G\n                    <jats:sub>M2<\/jats:sub>\n                    ganglioside within neurons throughout the central nervous system. The resulting neuronal cell death induces the primary symptoms of the disease: motor impairment, seizures, and sensory impairments. This study assesses the long-term effects of gene transfer in a Sandhoff (\u03b2-subunit knockout) mouse model. The study utilized a modified human \u03b2-hexosaminidase \u03b1-subunit (\u03bc-subunit) that contains critical sequences from the \u03b2-subunit that enables formation of a stable homodimer (HexM) and interaction with GM2AP to hydrolyze GM2 ganglioside. We investigated a self-complementary adeno-associated viral (scAAV) vector expressing HexM, through intravenous injections of the neonatal mice. We monitored one cohort for 8 weeks and another cohort long-term for survival benefit, behavioral, biochemical, and molecular analyses. Untreated Sandhoff disease (SD) control mice reached a humane endpoint at approximately 15 weeks, whereas treated mice had a median survival age of 40 weeks, an approximate 2.5-fold survival advantage. On behavioral tests, the treated mice outperformed their knockout age-matched controls and perform similarly to the heterozygous controls. Through the enzymatic and G\n                    <jats:sub>M2<\/jats:sub>\n                    ganglioside analyses, we observed a significant decrease in the G\n                    <jats:sub>M2<\/jats:sub>\n                    ganglioside level, even though the enzyme levels were not significantly increased. Molecular analyses revealed a global distribution of the vector between brain and spinal cord regions. In conclusion, the neonatal delivery of a novel viral vector expressing the human HexM enzyme is effective in ameliorating the SD mouse phenotype for long-term. Our data could have implications not only for treatment of SD but also for Tay\u2013Sachs disease (\u03b1-subunit deficiency) and similar brain disorders.\n                  <\/jats:p>","DOI":"10.1089\/hum.2016.015","type":"journal-article","created":{"date-parts":[[2016,5,20]],"date-time":"2016-05-20T05:59:39Z","timestamp":1463723979000},"page":"497-508","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":34,"title":["Systemic Gene Transfer of a Hexosaminidase Variant Using an scAAV9.47 Vector Corrects G\n                    <sub>M2<\/sub>\n                    Gangliosidosis in Sandhoff Mice"],"prefix":"10.1177","volume":"27","author":[{"given":"Karlaina J.L.","family":"Osmon","sequence":"first","affiliation":[{"name":"Queen's University","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan","family":"Woodley","sequence":"additional","affiliation":[{"name":"Queen's University","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Thompson","sequence":"additional","affiliation":[{"name":"Queen's University","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalina","family":"Ong","sequence":"additional","affiliation":[{"name":"Queen's University","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subha","family":"Karumuthil-Melethil","sequence":"additional","affiliation":[{"name":"University of North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John G.","family":"Keimel","sequence":"additional","affiliation":[{"name":"New Hope Research Foundation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Mark","sequence":"additional","affiliation":[{"name":"University of Manitoba","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Don","family":"Mahuran","sequence":"additional","affiliation":[{"name":"Genetics and Genome Biology, SickKids, Toronto, Ontario, Canada."},{"name":"University of Toronto","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J.","family":"Gray","sequence":"additional","affiliation":[{"name":"University of North Carolina"},{"name":"University of North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdeep S.","family":"Walia","sequence":"additional","affiliation":[{"name":"Queen's University","place":["Canada"]},{"name":"Queen's University","place":["Canada"]},{"name":"Queen's University","place":["Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2016,5,19]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.0822-13.2013"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.2183\/pjab.88.554"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.281.3.249"},{"key":"e_1_3_3_5_2","first-page":"161","article-title":"Genetic variants of Tay-Sachs disease: Tay-Sachs disease and Sandhoff's disease in French Canadians, juvenile Tay-Sachs disease in Lebanese Canadians, and a Tay-Sachs screening program in the French-Canadian population","volume":"18","author":"Andermann E","year":"1977","unstructured":"Andermann E, , Scriver CR, , Wolfe LS, et al. 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