{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T02:42:05Z","timestamp":1775011325377,"version":"3.50.1"},"reference-count":64,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T00:00:00Z","timestamp":1695772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Queen\u2019s University"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>GM2 gangliosidoses are a group of neurodegenerative lysosomal storage disorders that are characterized by the accumulation of GM2 gangliosides (GM2), leading to rapid neurological decline and death. The hydrolysis of GM2 requires the specific synthesis, processing, and combination of products of three genes\u2014HEXA, HEXB, and GM2A\u2014within the cell\u2019s lysosomes. Mutations in these genes result in Tay-Sachs disease, Sandhoff disease, or AB-variant GM2 gangliosidosis (ABGM2), respectively. ABGM2, the rarest of the three types, is characterized by a mutation in the GM2A gene, which encodes the GM2 activator (GM2A) protein. Being a monogenic disease, gene therapy is a plausible and likely effective method of treatment for ABGM2. This study aimed at assessing the effects of administering a one-time intravenous treatment of single-stranded Adeno-associated virus serotype 9 (ssAAV9)-GM2A viral vector at a dose of 1 \u00d7 1014 vector genomes (vg) per kilogram per mouse in an ABGM2 mouse model (Gm2a\u2212\/\u2212). ssAAV9-GM2A was administered at 1-day (neonatal) or 6-weeks of age (adult-stage). The results demonstrated that, in comparison to Gm2a\u2212\/\u2212 mice that received a vehicle injection, the treated mice had reduced GM2 accumulation within the central nervous system and had long-term persistence of vector genomes in the brain and liver. This proof-of-concept study is a step forward towards the development of a clinically therapeutic approach for the treatment of patients with ABGM2.<\/jats:p>","DOI":"10.3390\/ijms241914611","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T03:49:14Z","timestamp":1695786554000},"page":"14611","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Efficacy of Adeno-Associated Virus Serotype 9-Mediated Gene Therapy for AB-Variant GM2 Gangliosidosis"],"prefix":"10.3390","volume":"24","author":[{"given":"Meera","family":"Vyas","sequence":"first","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2306-2661","authenticated-orcid":false,"given":"Natalie M.","family":"Deschenes","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karlaina J. L.","family":"Osmon","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhilin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Imtiaz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shalini","family":"Kot","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Queen\u2019s University, Kingston, ON K7L 2V7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chris","family":"Richmond","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6240-8621","authenticated-orcid":false,"given":"Steven J.","family":"Gray","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, UT Southwestern Medical Center, Dallas, TX 75390, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jagdeep S.","family":"Walia","sequence":"additional","affiliation":[{"name":"Centre for Neuroscience Studies, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"},{"name":"Department of Biomedical and Molecular Sciences, Queen\u2019s University, Kingston, ON K7L 3N6, Canada"},{"name":"Department of Pediatrics, Queen\u2019s University, Kingston, ON K7L 2V7, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"136195","DOI":"10.1016\/j.neulet.2021.136195","article-title":"The GM2 gangliosidoses: Unlocking the mysteries of pathogenesis and treatment","volume":"764","author":"Toro","year":"2021","journal-title":"Neurosci. 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