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Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II.

Publication ,  Journal Article
Franco, LM; Sun, B; Yang, X; Bird, A; Zhang, H; Schneider, A; Brown, T; Young, SP; Clay, TM; Amalfitano, A; Chen, YT; Koeberl, DD
Published in: Mol Ther
November 2005

Glycogen storage disease type II (GSD-II; Pompe disease) is caused by a deficiency of acid alpha-glucosidase (GAA; acid maltase) and manifests as muscle weakness, hypertrophic cardiomyopathy, and respiratory failure. Adeno-associated virus vectors containing either a liver-specific promoter (LSP) (AAV-LSPhGAApA) or a hybrid CB promoter (AAV-CBhGAApA) to drive human GAA expression were pseudotyped as AAV8 and administered to immunocompetent GAA-knockout mice. Secreted hGAA was detectable in plasma between 1 day and 12 weeks postadministration with AAV-LSPhGAApA and only from 1 to 8 days postadministration for AAV-CBGAApA. No anti-GAA antibodies were detected in response to AAV-LSPhGAApA (<1:200), whereas AAV-CBhGAApA provoked an escalating antibody response starting 2 weeks postadministration. The LSP drove approximately 60-fold higher GAA expression than the CB promoter in the liver by 12 weeks following vector administration. Furthermore, the detected cellular immunity was provoked by AAV-CBhGAApA, as detected by ELISpot and CD4+/CD8+ lymphocyte immunodetection. GAA activity was increased to higher than normal and glycogen content was reduced to essentially normal levels in the heart and skeletal muscle following administration of AAV-LSPhGAApA. Therefore, liver-restricted GAA expression with an AAV vector evaded immunity and enhanced efficacy in GSD-II mice.

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Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

November 2005

Volume

12

Issue

5

Start / End Page

876 / 884

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Promoter Regions, Genetic
  • Plasmids
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice
  • Liver
  • Humans
  • Glycogen Storage Disease Type II
  • Glycogen
 

Citation

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Franco, L. M., Sun, B., Yang, X., Bird, A., Zhang, H., Schneider, A., … Koeberl, D. D. (2005). Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II. Mol Ther, 12(5), 876–884. https://doi.org/10.1016/j.ymthe.2005.04.024
Franco, Luis M., Baodong Sun, Xiaoyi Yang, Andrew Bird, Haoyue Zhang, Ayn Schneider, Talmage Brown, et al. “Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II.Mol Ther 12, no. 5 (November 2005): 876–84. https://doi.org/10.1016/j.ymthe.2005.04.024.
Franco LM, Sun B, Yang X, Bird A, Zhang H, Schneider A, et al. Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II. Mol Ther. 2005 Nov;12(5):876–84.
Franco, Luis M., et al. “Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II.Mol Ther, vol. 12, no. 5, Nov. 2005, pp. 876–84. Pubmed, doi:10.1016/j.ymthe.2005.04.024.
Franco LM, Sun B, Yang X, Bird A, Zhang H, Schneider A, Brown T, Young SP, Clay TM, Amalfitano A, Chen YT, Koeberl DD. Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II. Mol Ther. 2005 Nov;12(5):876–884.
Journal cover image

Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

November 2005

Volume

12

Issue

5

Start / End Page

876 / 884

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Promoter Regions, Genetic
  • Plasmids
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice
  • Liver
  • Humans
  • Glycogen Storage Disease Type II
  • Glycogen