In search of proof-of-concept: gene therapy for glycogen storage disease type Ia.
The emergence of life threatening long-term complications in glycogen storage disease type Ia (GSD-Ia) has emphasized the need for new therapies, such as gene therapy, which could achieve biochemical correction of glucose-6-phosphatase deficiency and reverse clinical involvement. We have developed gene therapy with a novel adeno-associated virus (AAV) vector that: 1) prevented mortality and corrected glycogen storage in the liver, 2) corrected hypoglycemia during fasting, and 3) achieved efficacy with a low number of vector particles in G6Pase-deficient mice and dogs. However, the gradual loss of transgene expression from episomal AAV vector genomes eventually necessitated the administration of a different pseudotype of the AAV vector to sustain dogs with GSD-Ia. Further preclinical development of AAV vector-mediated gene therapy is therefore warranted in GSD-Ia.
Division of Medical Genetics, Duke University Medical Center, Durham, NC, USA. koebe001@mc.duke.edu
Dwight D
DD
Koeberl
D000818:Animals; D000229:Dependovirus / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D005953:Glycogen Storage Disease Type I / Q000235:genetics* / Q000378:metabolism* / Q000628:therapy; D006801:Humans