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Glycogen storage disease (GSD) type Ia, caused by a deficiency of glucose\u20106\u2010phosphatase\u2010\u03b1, has been viewed as an outstanding candidate for gene therapy. This follow\u2010up report describes the long\u2010term outcome for the naturally occurring GSD\u2010Ia dogs treated with rAAV\u2010GPE\u2010hG6PC\u2010mediated gene therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of seven dogs were treated with rAAV\u2010GPE\u2010hG6PC\u2010mediated gene therapy. The first four dogs were treated at birth, and three dogs were treated between 2 and 6 months of age to assess the efficacy and safety in animals with mature livers. Blood and urine samples, radiographic studies, histological evaluation, and biodistribution were assessed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Gene therapy improved survival in the GSD\u2010Ia dogs. With treatment, the biochemical studies normalized for the duration of the study (up to 7 years). None of the rAAV\u2010GPE\u2010hG6PC\u2010treated dogs had focal hepatic lesions or renal abnormalities. Dogs treated at birth required a second dose of rAAV after 2\u20134 months; gene therapy after hepatic maturation resulted in improved efficacy after a single dose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>rAAV\u2010GPE\u2010hG6PC treatment in GSD\u2010Ia dogs was found to be safe and efficacious. GSD\u2010Ia is an attractive target for human gene therapy since it is a monogenic disorder with limited tissue involvement. Blood glucose and lactate monitoring can be used to assess effectiveness and as a biomarker of success. GSD\u2010Ia can also serve as a model for other hepatic monogenic disorders.<\/jats:p><\/jats:sec>","DOI":"10.1007\/s10545-018-0199-7","type":"journal-article","created":{"date-parts":[[2018,5,25]],"date-time":"2018-05-25T08:17:45Z","timestamp":1527236265000},"page":"977-984","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Long\u2010term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia"],"prefix":"10.1002","volume":"41","author":[{"given":"Young Mok","family":"Lee","sequence":"first","affiliation":[{"name":"Glycogen Storage Disease Program, Department of Pediatrics University of Connecticut School of Medicine Farmington CT 06030 USA"},{"name":"Glycogen Storage Disease Program University of Florida College of Medicine Gainesville FL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas 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