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dc.contributor.authorHocquemiller, Michaël
dc.contributor.authorGiersch, Laura
dc.contributor.authorMei, Xin
dc.contributor.authorGross, Amanda L
dc.contributor.authorRandle, Ashley N
dc.contributor.authorGray-Edwards, Heather L
dc.contributor.authorHudson, Judith A
dc.contributor.authorTodeasa, Sophia
dc.contributor.authorStoica, Lorelei
dc.contributor.authorMartin, Douglas R
dc.contributor.authorSena-Esteves, Miguel
dc.contributor.authorAiach, Karen
dc.contributor.authorLaufer, Ralph
dc.date.accessioned2023-01-24T14:31:31Z
dc.date.available2023-01-24T14:31:31Z
dc.date.issued2022-10-07
dc.identifier.citationHocquemiller M, Giersch L, Mei X, Gross AL, Randle AN, Gray-Edwards HL, Hudson JA, Todeasa S, Stoica L, Martin DR, Sena-Esteves M, Aiach K, Laufer R. AAVrh10 vector corrects pathology in animal models of GM1 gangliosidosis and achieves widespread distribution in the CNS of nonhuman primates. Mol Ther Methods Clin Dev. 2022 Oct 7;27:281-292. doi: 10.1016/j.omtm.2022.10.004. PMID: 36320411; PMCID: PMC9594110.en_US
dc.identifier.issn2329-0501
dc.identifier.doi10.1016/j.omtm.2022.10.004en_US
dc.identifier.pmid36320411
dc.identifier.urihttp://hdl.handle.net/20.500.14038/51580
dc.description.abstractGM1 gangliosidosis is a rare, inherited neurodegenerative disorder caused by mutations in the GLB1 gene, which encodes the lysosomal hydrolase acid β-galactosidase (β-gal). β-gal deficiency leads to toxic accumulation of GM1 ganglioside, predominantly in the central nervous system (CNS), resulting in progressive neurodegeneration. LYS-GM101 is an AAVrh.10-based gene therapy vector carrying the human GLB1 cDNA. The efficacy of intra-cerebrospinal fluid injection of LYS-GM101 analogs was demonstrated in GM1 mouse and cat models with widespread diffusion of β-gal and correction of GM1 ganglioside accumulation in the CNS without observable adverse effects. Clinical dose selection was performed, based on a good-laboratory-practice study, in nonhuman primates (NHPs) using the clinical LYS-GM101 vector. A broadly distributed increase of β-gal activity was observed in NHP brain 3 months after intra-cisterna magna injection of LYS-GM101 at 1.0 × 1012 vg/mL CSF and 4.0 × 1012 vg/mL CSF, with 20% and 60% increases compared with vehicle-treated animals, respectively. Histopathologic examination revealed asymptomatic adverse changes in the sensory pathways of the spinal cord and dorsal root ganglia in both sexes and at both doses. Taken as a whole, these pre-clinical data support the initiation of a clinical study with LYS-GM101 for the treatment of GM1 gangliosidosis.en_US
dc.language.isoenen_US
dc.relation.ispartofMolecular Therapy – Methods & Clinical Developmenten_US
dc.relation.urlhttps://doi.org/10.1016/j.omtm.2022.10.004en_US
dc.rightsCopyright 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/); Attribution-NonCommercial-NoDerivatives 4.0 Internationalen_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/*
dc.subjectAAVen_US
dc.subjectGM1en_US
dc.subjectgangliosidosisen_US
dc.subjectgene therapyen_US
dc.subjectlysosomal storage diseaseen_US
dc.titleAAVrh10 vector corrects pathology in animal models of GM1 gangliosidosis and achieves widespread distribution in the CNS of nonhuman primatesen_US
dc.typeJournal Articleen_US
dc.source.journaltitleMolecular therapy. Methods & clinical development
dc.source.volume27
dc.source.beginpage281
dc.source.endpage292
dc.source.countryUnited States
dc.identifier.journalMolecular therapy. Methods & clinical development
refterms.dateFOA2023-01-24T14:31:32Z
dc.contributor.departmentHorae Gene Therapy Centeren_US
dc.contributor.departmentNeurologyen_US
dc.contributor.departmentRadiologyen_US


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Copyright 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/); Attribution-NonCommercial-NoDerivatives 4.0 International
Except where otherwise noted, this item's license is described as Copyright 2022 The Authors. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/); Attribution-NonCommercial-NoDerivatives 4.0 International