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Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice.

Publication ,  Journal Article
Kiang, A; Hartman, ZC; Liao, S; Xu, F; Serra, D; Palmer, DJ; Ng, P; Amalfitano, A
Published in: Mol Ther
January 2006

Glycogen storage disease type II (GSD-II) patients manifest symptoms of muscular dystrophy secondary to abnormal glycogen storage in cardiac and skeletal muscles. For GSD-II, we hypothesized that a fully deleted adenovirus (FDAd) vector expressing hGAA via nonviral regulatory elements (PEPCK promoter/ApoE enhancer) would facilitate long-term efficacy and decrease propensity to generate anti-hGAA antibody responses against hepatically secreted hGAA. Intravenous delivery of FDAdhGAA into GAA-tolerant or nontolerant GAA-KO mice resulted in long-term hepatic secretion of hGAA. Specifically, nontolerant mice achieved complete reversal of cardiac glycogen storage and near-complete skeletal glycogen correction for at least 180 days and tolerant mice for minimally 300 days coupled with the preservation of muscle strength. Anti-hGAA antibody levels in both mouse strains were significantly less relative to those previously generated by CMV-driven hGAA expression in nontolerant GAA-KO mice. However, plasma GAA levels decreased in nontolerant GAA-KO mice despite long-term intrahepatic GAA expression from the persistent vector. This intriguing result is discussed in light of other examples of "tolerance" induction by gene-transfer-based approaches.

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Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

January 2006

Volume

13

Issue

1

Start / End Page

127 / 134

Location

United States

Related Subject Headings

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

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Kiang, A., Hartman, Z. C., Liao, S., Xu, F., Serra, D., Palmer, D. J., … Amalfitano, A. (2006). Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice. Mol Ther, 13(1), 127–134. https://doi.org/10.1016/j.ymthe.2005.08.006
Kiang, Anne, Zachary C. Hartman, Shaoxi Liao, Fang Xu, Delila Serra, Donna J. Palmer, Philip Ng, and Andrea Amalfitano. “Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice.Mol Ther 13, no. 1 (January 2006): 127–34. https://doi.org/10.1016/j.ymthe.2005.08.006.
Kiang, Anne, et al. “Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice.Mol Ther, vol. 13, no. 1, Jan. 2006, pp. 127–34. Pubmed, doi:10.1016/j.ymthe.2005.08.006.
Kiang A, Hartman ZC, Liao S, Xu F, Serra D, Palmer DJ, Ng P, Amalfitano A. Fully deleted adenovirus persistently expressing GAA accomplishes long-term skeletal muscle glycogen correction in tolerant and nontolerant GSD-II mice. Mol Ther. 2006 Jan;13(1):127–134.
Journal cover image

Published In

Mol Ther

DOI

ISSN

1525-0016

Publication Date

January 2006

Volume

13

Issue

1

Start / End Page

127 / 134

Location

United States

Related Subject Headings

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