ArticleHuman gene therapy2012
Long-term efficacy following readministration of an adeno-associated virus vector in dogs with glycogen storage disease type Ia.
Article in Human gene therapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Synergism of dual AAV gene therapy and rapamycin rescues GSDIII phenotype in muscle and liver.JCI insight · 2024Article
- A splice-switching oligonucleotide treatment ameliorates glycogen storage disease type 1a in mice with G6PC c.648G>T.The Journal of clinical investigation · 2023Article
- Genome editing usingMolecular therapy. Methods & clinical development · 2023Article
- Glycogen storage disease type I: Genetic etiology, clinical manifestations, and conventional and gene therapies.Pediatric discovery · 2023Article
- Virally Mediated Connexin 26 Expression in Postnatal Scala Media Significantly and Transiently Preserves Hearing in Connexin 30 Null Mice.Frontiers in cell and developmental biology · 2022Article
- Links between autophagy and disorders of glycogen metabolism - Perspectives on pathogenesis and possible treatments.Molecular genetics and metabolism · 2020Review
- Pathogenesis of Hepatic Tumors following Gene Therapy in Murine and Canine Models of Glycogen Storage Disease.Molecular therapy. Methods & clinical development · 2019Article
- Immunomodulatory, liver depot gene therapy for Pompe disease.Cellular immunology · 2019Review
- Bezafibrate Enhances AAV Vector-Mediated Genome Editing in Glycogen Storage Disease Type Ia.Molecular therapy. Methods & clinical development · 2019Article
- An evolutionary approach to optimizing glucose-6-phosphatase-α enzymatic activity for gene therapy of glycogen storage disease type Ia.Journal of inherited metabolic disease · 2019Article
- Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia.Human molecular genetics · 2019Article
- Long-term safety and efficacy of AAV gene therapy in the canine model of glycogen storage disease type Ia.Journal of inherited metabolic disease · 2018Article
- Long-term complications of glycogen storage disease type Ia in the canine model treated with gene replacement therapy.Journal of inherited metabolic disease · 2018Article
- Emerging Issues in AAV-MediatedMolecular therapy. Methods & clinical development · 2018Review
- G6PC mRNA Therapy Positively Regulates Fasting Blood Glucose and Decreases Liver Abnormalities in a Mouse Model of Glycogen Storage Disease 1a.Molecular therapy : the journal of the American Society of Gene Therapy · 2018Article
- Hepatic mitochondrial dysfunction is a feature of Glycogen Storage Disease Type Ia (GSDIa).Scientific reports · 2017Article
- In Vivo Zinc Finger Nuclease-mediated Targeted Integration of a Glucose-6-phosphatase Transgene Promotes Survival in Mice With Glycogen Storage Disease Type IA.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- Successful Phenotype Improvement following Gene Therapy for Severe Hemophilia A in Privately Owned Dogs.PloS one · 2016Article
- Large animal models and new therapies for glycogen storage disease.Journal of inherited metabolic disease · 2015Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Glycogen storage disease type Ia (GSD-Ia) is the inherited deficiency of glucose-6-phosphatase (G6Pase), primarily found in liver and kidney, which causes life-threatening hypoglycemia. Dogs with GSD-Ia were treated with double-stranded adeno-associated virus (AAV) vectors encoding human G6Pase. Administration of an AAV9 pseudotyped (AAV2/9) vector to seven consecutive GSD-Ia neonates prevented hypoglycemia during fasting for up to 8 hr; however, efficacy eventually waned between 2 and 30 months of age, and readministration of a new pseudotype was eventually required to maintain control of hypoglycemia. Three of these dogs succumbed to acute hypoglycemia between 7 and 9 weeks of age; however, this demise could have been prevented by earlier readministration an AAV vector, as demonstrated by successful prevention of mortality of three dogs treated earlier in life. Over the course of this study, six out of nine dogs survived after readministration of an AAV vector. Of these, each dog required readministration on average every 9 months. However, two were not retreated until >34 months of age, while one with preexisting antibodies was re-treated three times in 10 months. Glycogen content was normalized in the liver following vector administration, and G6Pase activity was increased in the liver of vector-treated dogs in comparison with GSD-Ia dogs that received only with dietary treatment. G6Pase activity reached approximately 40% of normal in two female dogs following AAV2/9 vector administration. Elevated aspartate transaminase in absence of inflammation indicated that hepatocellular turnover in the liver might drive the loss of vector genomes. Survival was prolonged for up to 60 months in dogs treated by readministration, and all dogs treated by readministration continue to thrive despite the demonstrated risk for recurrent hypoglycemia and mortality from waning efficacy of the AAV2/9 vector. These preclinical data support the further translation of AAV vector-mediated gene therapy in GSD-Ia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.