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dc.contributor.authorKeeler, Allison M
dc.contributor.authorZieger, Marina
dc.contributor.authorTodeasa, Sophia H.
dc.contributor.authorMcCall, Angela L.
dc.contributor.authorGifford, Jennifer C.
dc.contributor.authorBirsak, Samantha
dc.contributor.authorChoudhury, Sourav Roy
dc.contributor.authorByrne, Barry J.
dc.contributor.authorSena-Esteves, Miguel
dc.contributor.authorElmallah, Mai K.
dc.date2022-08-11T08:10:13.000
dc.date.accessioned2022-08-23T16:59:43Z
dc.date.available2022-08-23T16:59:43Z
dc.date.issued2018-07-25
dc.date.submitted2018-08-13
dc.identifier.citation<p>Hum Gene Ther. 2018 Jul 25. doi: 10.1089/hum.2018.016. [Epub ahead of print] <a href="https://doi.org/10.1089/hum.2018.016">Link to article on publisher's site</a></p>
dc.identifier.issn1043-0342 (Linking)
dc.identifier.doi10.1089/hum.2018.016
dc.identifier.pmid29901418
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43653
dc.description.abstractPompe disease is an autosomal recessive glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disruption in muscle and the central nervous system (CNS). Adeno-associated virus (AAV) gene therapy is ideal for Pompe disease, since a single systemic injection may correct both muscle and CNS pathologies. Using the Pompe mouse (B6;129-Gaa(Tm1Rabn)/J), this study sought to explore if AAVB1, a newly engineered vector with a high affinity for muscle and CNS, reduces systemic weakness and improves survival in adult mice. Three-month-old Gaa(-/-) animals were injected with either AAVB1 or AAV9 vectors expressing GAA and tissues were harvested 6 months later. Both AAV vectors prolonged survival. AAVB1-treated animals had a robust weight gain compared to the AAV9-treated group. Vector genome levels, GAA enzyme activity, and histological analysis indicated that both vectors transduced the heart efficiently, leading to glycogen clearance, and transduced the diaphragm and CNS at comparable levels. AAVB1-treated mice had higher GAA activity and greater glycogen clearance in the tongue. Finally, AAVB1-treated animals showed improved respiratory function comparable to wild-type animals. In conclusion, AAVB1-GAA offers a promising therapeutic option for the treatment of muscle and CNS in Pompe disease.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=29901418&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.1089/hum.2018.016
dc.subjectAAV9
dc.subjectAAVB1
dc.subjectPompe disease
dc.subjectglycogen
dc.subjectrespiratory
dc.subjectCongenital, Hereditary, and Neonatal Diseases and Abnormalities
dc.subjectEnzymes and Coenzymes
dc.subjectGenetics and Genomics
dc.subjectNervous System Diseases
dc.subjectNutritional and Metabolic Diseases
dc.subjectTherapeutics
dc.titleSystemic Delivery of AAVB1-GAA Clears Glycogen and Prolongs Survival in a Mouse Model of Pompe Disease
dc.typeJournal Article
dc.source.journaltitleHuman gene therapy
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/peds_pp/226
dc.identifier.contextkey12647330
html.description.abstract<p>Pompe disease is an autosomal recessive glycogen storage disorder caused by deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). GAA deficiency results in systemic lysosomal glycogen accumulation and cellular disruption in muscle and the central nervous system (CNS). Adeno-associated virus (AAV) gene therapy is ideal for Pompe disease, since a single systemic injection may correct both muscle and CNS pathologies. Using the Pompe mouse (B6;129-Gaa(Tm1Rabn)/J), this study sought to explore if AAVB1, a newly engineered vector with a high affinity for muscle and CNS, reduces systemic weakness and improves survival in adult mice. Three-month-old Gaa(-/-) animals were injected with either AAVB1 or AAV9 vectors expressing GAA and tissues were harvested 6 months later. Both AAV vectors prolonged survival. AAVB1-treated animals had a robust weight gain compared to the AAV9-treated group. Vector genome levels, GAA enzyme activity, and histological analysis indicated that both vectors transduced the heart efficiently, leading to glycogen clearance, and transduced the diaphragm and CNS at comparable levels. AAVB1-treated mice had higher GAA activity and greater glycogen clearance in the tongue. Finally, AAVB1-treated animals showed improved respiratory function comparable to wild-type animals. In conclusion, AAVB1-GAA offers a promising therapeutic option for the treatment of muscle and CNS in Pompe disease.</p>
dc.identifier.submissionpathpeds_pp/226
dc.contributor.departmentDepartment of Neurology
dc.contributor.departmentHorae Gene Therapy Center
dc.contributor.departmentDivision of Pulmonary Medicine, Department of Pediatrics


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