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Efficacy of helper-dependent adenovirus vector-mediated gene therapy in murine glycogen storage disease type Ia.

Publication ,  Journal Article
Koeberl, DD; Sun, B; Bird, A; Chen, YT; Oka, K; Chan, L
Published in: Mol Ther
July 2007

Genetic deficiency of glucose-6-phosphatase (G6Pase) underlies glycogen storage disease type Ia (GSD-Ia, also known as von Gierke disease; MIM 232200), an autosomal recessive disorder of metabolism associated with life-threatening hypoglycemia and growth retardation. We tested whether helper-dependent adenovirus (HDAd)-mediated hepatic delivery of G6Pase would lead to prolonged survival and sustained correction of the metabolic abnormalities in G6Pase knockout (KO) mice, a model for a severe form of GSD-Ia. An HDAd vector encoding G6Pase was administered intravenously (2 or 5 x 10(12)vector particles/kg) to 2-week-old (w.o.) G6Pase-KO mice. Following HDAd vector administration survival was prolonged to a median of 7 months, in contrast to untreated affected mice that did not survive past 3 weeks of age. G6Pase levels increased more than tenfold between 3 days and 28 weeks after HDAd injection (P < 0.03). The weights of untreated 2 w.o. G6Pase-KO mice were approximately half those of their unaffected littermates, and treatment stimulated their growth to the size of wild-type mice. Severe hypoglycemia and hypercholesterolemia, which are hallmarks of GSD-Ia both in humans and in mice, were also restored to normalcy by the treatment. Glycogen accumulation in the liver was markedly reduced. The efficacy of HDAd-G6Pase treatment in reversing the physiological and biochemical abnormalities associated with GSD-Ia in affected G6Pase-KO mice justifies further preclinical evaluation in murine and canine models of GSD-Ia.

Duke Scholars

Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

July 2007

Volume

15

Issue

7

Start / End Page

1253 / 1258

Location

United States

Related Subject Headings

  • Mice, Knockout
  • Mice
  • Liver
  • Glycogen Storage Disease Type I
  • Glycogen
  • Glucose-6-Phosphatase
  • Genetic Vectors
  • Genetic Therapy
  • Biotechnology
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
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Koeberl, D. D., Sun, B., Bird, A., Chen, Y. T., Oka, K., & Chan, L. (2007). Efficacy of helper-dependent adenovirus vector-mediated gene therapy in murine glycogen storage disease type Ia. Mol Ther, 15(7), 1253–1258. https://doi.org/10.1038/sj.mt.6300188
Koeberl, Dwight D., B. Sun, A. Bird, Y. T. Chen, K. Oka, and L. Chan. “Efficacy of helper-dependent adenovirus vector-mediated gene therapy in murine glycogen storage disease type Ia.Mol Ther 15, no. 7 (July 2007): 1253–58. https://doi.org/10.1038/sj.mt.6300188.
Koeberl DD, Sun B, Bird A, Chen YT, Oka K, Chan L. Efficacy of helper-dependent adenovirus vector-mediated gene therapy in murine glycogen storage disease type Ia. Mol Ther. 2007 Jul;15(7):1253–8.
Koeberl, Dwight D., et al. “Efficacy of helper-dependent adenovirus vector-mediated gene therapy in murine glycogen storage disease type Ia.Mol Ther, vol. 15, no. 7, July 2007, pp. 1253–58. Pubmed, doi:10.1038/sj.mt.6300188.
Koeberl DD, Sun B, Bird A, Chen YT, Oka K, Chan L. Efficacy of helper-dependent adenovirus vector-mediated gene therapy in murine glycogen storage disease type Ia. Mol Ther. 2007 Jul;15(7):1253–1258.

Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

July 2007

Volume

15

Issue

7

Start / End Page

1253 / 1258

Location

United States

Related Subject Headings

  • Mice, Knockout
  • Mice
  • Liver
  • Glycogen Storage Disease Type I
  • Glycogen
  • Glucose-6-Phosphatase
  • Genetic Vectors
  • Genetic Therapy
  • Biotechnology
  • Animals