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Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-alpha-glucosidase.

Publication ,  Journal Article
Amalfitano, A; McVie-Wylie, AJ; Hu, H; Dawson, TL; Raben, N; Plotz, P; Chen, YT
Published in: Proc Natl Acad Sci U S A
August 3, 1999

This report demonstrates that a single intravenous administration of a gene therapy vector can potentially result in the correction of all affected muscles in a mouse model of a human genetic muscle disease. These results were achieved by capitalizing both on the positive attributes of modified adenovirus-based vectoring systems and receptor-mediated lysosomal targeting of enzymes. The muscle disease treated, glycogen storage disease type II, is a lysosomal storage disorder that manifests as a progressive myopathy, secondary to massive glycogen accumulations in the skeletal and/or cardiac muscles of affected individuals. We demonstrated that a single intravenous administration of a modified Ad vector encoding human acid alpha-glucosidase (GAA) resulted in efficient hepatic transduction and secretion of high levels of the precursor GAA proenzyme into the plasma of treated animals. Subsequently, systemic distribution and uptake of the proenzyme into the skeletal and cardiac muscles of the GAA-knockout mouse was confirmed. As a result, systemic decreases (and correction) of the glycogen accumulations in a variety of muscle tissues was demonstrated. This model can potentially be expanded to include the treatment of other lysosomal enzyme disorders. Lessons learned from systemic genetic therapy of muscle disorders also should have implications for other muscle diseases, such as the muscular dystrophies.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 3, 1999

Volume

96

Issue

16

Start / End Page

8861 / 8866

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Promoter Regions, Genetic
  • Muscular Diseases
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Liver
  • Humans
  • Glycogen Storage Disease Type II
 

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Amalfitano, A., McVie-Wylie, A. J., Hu, H., Dawson, T. L., Raben, N., Plotz, P., & Chen, Y. T. (1999). Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-alpha-glucosidase. Proc Natl Acad Sci U S A, 96(16), 8861–8866. https://doi.org/10.1073/pnas.96.16.8861
Amalfitano, A., A. J. McVie-Wylie, H. Hu, T. L. Dawson, N. Raben, P. Plotz, and Y. T. Chen. “Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-alpha-glucosidase.Proc Natl Acad Sci U S A 96, no. 16 (August 3, 1999): 8861–66. https://doi.org/10.1073/pnas.96.16.8861.
Amalfitano A, McVie-Wylie AJ, Hu H, Dawson TL, Raben N, Plotz P, et al. Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-alpha-glucosidase. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8861–6.
Amalfitano, A., et al. “Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-alpha-glucosidase.Proc Natl Acad Sci U S A, vol. 96, no. 16, Aug. 1999, pp. 8861–66. Pubmed, doi:10.1073/pnas.96.16.8861.
Amalfitano A, McVie-Wylie AJ, Hu H, Dawson TL, Raben N, Plotz P, Chen YT. Systemic correction of the muscle disorder glycogen storage disease type II after hepatic targeting of a modified adenovirus vector encoding human acid-alpha-glucosidase. Proc Natl Acad Sci U S A. 1999 Aug 3;96(16):8861–8866.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

August 3, 1999

Volume

96

Issue

16

Start / End Page

8861 / 8866

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Promoter Regions, Genetic
  • Muscular Diseases
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice, Inbred C57BL
  • Mice
  • Liver
  • Humans
  • Glycogen Storage Disease Type II