Skip to main content

Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.

Publication ,  Journal Article
Luo, X; Hall, G; Li, S; Bird, A; Lavin, PJ; Winn, MP; Kemper, AR; Brown, TT; Koeberl, DD
Published in: Mol Ther
November 2011

Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg/dl) was prevented for >6 months by the dsAAV2/7, dsAAV2/8, and dsAAV2/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2/7 and dsAAV2/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2/9 vector. Hepatorenal correction in G6pase (-/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

November 2011

Volume

19

Issue

11

Start / End Page

1961 / 1970

Location

United States

Related Subject Headings

  • Mice, Knockout
  • Mice
  • Male
  • Liver
  • Kidney
  • Kaplan-Meier Estimate
  • Hypoglycemia
  • Humans
  • Glycogen Storage Disease Type I
  • Glucose-6-Phosphatase
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Luo, X., Hall, G., Li, S., Bird, A., Lavin, P. J., Winn, M. P., … Koeberl, D. D. (2011). Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector. Mol Ther, 19(11), 1961–1970. https://doi.org/10.1038/mt.2011.126
Luo, Xiaoyan, Gentzon Hall, Songtao Li, Andrew Bird, Peter J. Lavin, Michelle P. Winn, Alex R. Kemper, Talmage T. Brown, and Dwight D. Koeberl. “Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.Mol Ther 19, no. 11 (November 2011): 1961–70. https://doi.org/10.1038/mt.2011.126.
Luo X, Hall G, Li S, Bird A, Lavin PJ, Winn MP, et al. Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector. Mol Ther. 2011 Nov;19(11):1961–70.
Luo, Xiaoyan, et al. “Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.Mol Ther, vol. 19, no. 11, Nov. 2011, pp. 1961–70. Pubmed, doi:10.1038/mt.2011.126.
Luo X, Hall G, Li S, Bird A, Lavin PJ, Winn MP, Kemper AR, Brown TT, Koeberl DD. Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector. Mol Ther. 2011 Nov;19(11):1961–1970.

Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

November 2011

Volume

19

Issue

11

Start / End Page

1961 / 1970

Location

United States

Related Subject Headings

  • Mice, Knockout
  • Mice
  • Male
  • Liver
  • Kidney
  • Kaplan-Meier Estimate
  • Hypoglycemia
  • Humans
  • Glycogen Storage Disease Type I
  • Glucose-6-Phosphatase