{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Taghian T"],"funding":["UMass Chan Medical School","National Tay-Sachs and Allied Diseases Association","Scott-Ritchey Research Center","NINDS NIH HHS","NIH"],"pagination":["e182942"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12646665"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["135(23)"],"pubmed_abstract":["Tay-Sachs disease (TSD) and Sandhoff disease are fatal neurodegenerative diseases without an effective therapy that are caused by mutations in the HEXA and HEXB genes, respectively. Together they encode the heterodimeric isozyme of hexosaminidase, hexosaminidase A (HexA), that degrades GM2 ganglioside. This report describes a 5-year-long study using a bidirectional adeno-associated virus 9 (AAV9) vector (AAV9-Bic_HexA/HexB) encoding both HEXA and HEXB in the TSD sheep model. Bidirectional AAV9 was delivered i.v. or through various cerebrospinal fluid (CSF) delivery routes: intracerebroventricular (ICV), cisterna magna (CM), and lumbar intrathecal space (LIT). The longest survival and best distribution were achieved by multipoint CSF delivery (combined CM, ICV, and LIT) with treated animals"],"journal":["The Journal of clinical investigation"],"pubmed_title":["Five-year analysis of efficacy and safety of a bidirectional AAV gene therapy in Tay-Sachs sheep."],"pmcid":["PMC12646665"],"funding_grant_id":["NA","K08NS096219","K08 NS096219"],"pubmed_authors":["Benatti HR","Lopez Y","Taghian T","Johnson S","Gao G","Esteves S","Lahey HG","Pulaparthi S","Gately R","Su Q","Puri A","Gounis MJ","McCarthy JT","Baker WC","Jiang X","Xie J","Gallagher J","Hall E","Anagnostakou V","Lopez Mercado K","Mather S","Taylor A","McElroy A","Fernau D","King R","Koehler J","Gray-Edwards H","Bierfeldt L","Batista AR","Bertrand S","Parsley E","Prestigiacomo R","Martin DR","Gross A","Tuominen S","Sena-Esteves M","Diffie E"],"additional_accession":[]},"is_claimable":false,"name":"Five-year analysis of efficacy and safety of a bidirectional AAV gene therapy in Tay-Sachs sheep.","description":"Tay-Sachs disease (TSD) and Sandhoff disease are fatal neurodegenerative diseases without an effective therapy that are caused by mutations in the HEXA and HEXB genes, respectively. Together they encode the heterodimeric isozyme of hexosaminidase, hexosaminidase A (HexA), that degrades GM2 ganglioside. This report describes a 5-year-long study using a bidirectional adeno-associated virus 9 (AAV9) vector (AAV9-Bic_HexA/HexB) encoding both HEXA and HEXB in the TSD sheep model. Bidirectional AAV9 was delivered i.v. or through various cerebrospinal fluid (CSF) delivery routes: intracerebroventricular (ICV), cisterna magna (CM), and lumbar intrathecal space (LIT). The longest survival and best distribution were achieved by multipoint CSF delivery (combined CM, ICV, and LIT) with treated animals","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Dec","modification":"2026-06-05T19:14:14.102Z","creation":"2026-05-20T03:14:55.034Z"},"accession":"S-EPMC12646665","cross_references":{"pubmed":["41026525"],"doi":["10.1172/JCI182942"]}}