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dc.contributor.authorFlotte, Terence R.
dc.contributor.authorCataltepe, Oguz
dc.contributor.authorPuri, Ajit S.
dc.contributor.authorBatista, Ana Rita
dc.contributor.authorMoser, Richard P.
dc.contributor.authorMcKenna-Yasek, Diane
dc.contributor.authorDouthwright, Catherine
dc.contributor.authorGernoux, Gwladys
dc.contributor.authorBlackwood, Meghan
dc.contributor.authorMueller, Christian
dc.contributor.authorTai, Phillip W. L.
dc.contributor.authorBateman, Scot T.
dc.contributor.authorSpanakis, Spiro G.
dc.contributor.authorParzych, Julia
dc.contributor.authorKeeler, Allison M.
dc.contributor.authorAbayazeed, Aly
dc.contributor.authorRohatgi, Saurabh
dc.contributor.authorGibson, Laura L.
dc.contributor.authorFinberg, Robert W.
dc.contributor.authorBarton, Bruce A.
dc.contributor.authorVardar, Zeynep
dc.contributor.authorShazeeb, Mohammed S.
dc.contributor.authorGounis, Matthew J.
dc.contributor.authorBrown, Robert H. Jr.
dc.contributor.authorGray-Edwards, Heather L
dc.contributor.authorSena-Esteves, Miguel
dc.date2022-08-11T08:10:50.000
dc.date.accessioned2022-08-23T17:21:54Z
dc.date.available2022-08-23T17:21:54Z
dc.date.issued2022-02-10
dc.date.submitted2022-05-03
dc.identifier.citation<p>Flotte TR, Cataltepe O, Puri A, Batista AR, Moser R, McKenna-Yasek D, Douthwright C, Gernoux G, Blackwood M, Mueller C, Tai PWL, Jiang X, Bateman S, Spanakis SG, Parzych J, Keeler AM, Abayazeed A, Rohatgi S, Gibson L, Finberg R, Barton BA, Vardar Z, Shazeeb MS, Gounis M, Tifft CJ, Eichler FS, Brown RH Jr, Martin DR, Gray-Edwards HL, Sena-Esteves M. AAV gene therapy for Tay-Sachs disease. Nat Med. 2022 Feb;28(2):251-259. doi: 10.1038/s41591-021-01664-4. Epub 2022 Feb 10. PMID: 35145305. <a href="https://doi.org/10.1038/s41591-021-01664-4">Link to article on publisher's site</a></p>
dc.identifier.issn1078-8956 (Linking)
dc.identifier.doi10.1038/s41591-021-01664-4
dc.identifier.pmid35145305
dc.identifier.urihttp://hdl.handle.net/20.500.14038/48628
dc.description<p>Full author list omitted for brevity. For the full list of authors, see article.</p>
dc.description.abstractTay-Sachs disease (TSD) is an inherited neurological disorder caused by deficiency of hexosaminidase A (HexA). Here, we describe an adeno-associated virus (AAV) gene therapy expanded-access trial in two patients with infantile TSD (IND 18225) with safety as the primary endpoint and no secondary endpoints. Patient TSD-001 was treated at 30 months with an equimolar mix of AAVrh8-HEXA and AAVrh8-HEXB administered intrathecally (i.t.), with 75% of the total dose (1 x 10(14) vector genomes (vg)) in the cisterna magna and 25% at the thoracolumbar junction. Patient TSD-002 was treated at 7 months by combined bilateral thalamic (1.5 x 10(12) vg per thalamus) and i.t. infusion (3.9 x 10(13) vg). Both patients were immunosuppressed. Injection procedures were well tolerated, with no vector-related adverse events (AEs) to date. Cerebrospinal fluid (CSF) HexA activity increased from baseline and remained stable in both patients. TSD-002 showed disease stabilization by 3 months after injection with ongoing myelination, a temporary deviation from the natural history of infantile TSD, but disease progression was evident at 6 months after treatment. TSD-001 remains seizure-free at 5 years of age on the same anticonvulsant therapy as before therapy. TSD-002 developed anticonvulsant-responsive seizures at 2 years of age. This study provides early safety and proof-of-concept data in humans for treatment of patients with TSD by AAV gene therapy.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=35145305&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1038/s41591-021-01664-4
dc.subjectGenetic vectors
dc.subjectNeurodegenerative diseases
dc.subjectCongenital, Hereditary, and Neonatal Diseases and Abnormalities
dc.subjectGenetics and Genomics
dc.subjectNervous System Diseases
dc.subjectNeurology
dc.subjectRadiology
dc.subjectTherapeutics
dc.titleAAV gene therapy for Tay-Sachs disease
dc.typeJournal Article
dc.source.journaltitleNature medicine
dc.source.volume28
dc.source.issue2
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/radiology_pubs/691
dc.identifier.contextkey28980195
html.description.abstract<p>Tay-Sachs disease (TSD) is an inherited neurological disorder caused by deficiency of hexosaminidase A (HexA). Here, we describe an adeno-associated virus (AAV) gene therapy expanded-access trial in two patients with infantile TSD (IND 18225) with safety as the primary endpoint and no secondary endpoints. Patient TSD-001 was treated at 30 months with an equimolar mix of AAVrh8-HEXA and AAVrh8-HEXB administered intrathecally (i.t.), with 75% of the total dose (1 x 10(14) vector genomes (vg)) in the cisterna magna and 25% at the thoracolumbar junction. Patient TSD-002 was treated at 7 months by combined bilateral thalamic (1.5 x 10(12) vg per thalamus) and i.t. infusion (3.9 x 10(13) vg). Both patients were immunosuppressed. Injection procedures were well tolerated, with no vector-related adverse events (AEs) to date. Cerebrospinal fluid (CSF) HexA activity increased from baseline and remained stable in both patients. TSD-002 showed disease stabilization by 3 months after injection with ongoing myelination, a temporary deviation from the natural history of infantile TSD, but disease progression was evident at 6 months after treatment. TSD-001 remains seizure-free at 5 years of age on the same anticonvulsant therapy as before therapy. TSD-002 developed anticonvulsant-responsive seizures at 2 years of age. This study provides early safety and proof-of-concept data in humans for treatment of patients with TSD by AAV gene therapy.</p>
dc.identifier.submissionpathradiology_pubs/691
dc.contributor.departmentPopulation and Quantitative Health Sciences
dc.contributor.departmentMedicine
dc.contributor.departmentAnesthesiology and Perioperative Medicine
dc.contributor.departmentNeurology
dc.contributor.departmentNeurosurgery
dc.contributor.departmentLi Weibo Institute for Rare Diseases Research
dc.contributor.departmentHorae Gene Therapy Center
dc.contributor.departmentPediatrics
dc.contributor.departmentRadiology
dc.source.pages251-259


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