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Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy.

Publication ,  Journal Article
Sun, B; Young, SP; Li, P; Di, C; Brown, T; Salva, MZ; Li, S; Bird, A; Yan, Z; Auten, R; Hauschka, SD; Koeberl, DD
Published in: Mol Ther
August 2008

Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the deficiency of acid alpha-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. An adeno-associated virus 2/8 (AAV2/8) vector containing the muscle creatine kinase (MCK) (CK1) reduced glycogen content by approximately 50% in the heart and quadriceps in GAA-knockout (GAA-KO) mice; furthermore, an AAV2/8 vector containing the hybrid alpha-myosin heavy chain enhancer-/MCK enhancer-promoter (MHCK7) cassette reduced glycogen content by >95% in heart and >75% in the diaphragm and quadriceps. Transduction with an AAV2/8 vector was higher in the quadriceps than in the gastrocnemius. An AAV2/9 vector containing the MHCK7 cassette corrected GAA deficiency in the distal hindlimb, and glycogen accumulations were substantially cleared by human GAA (hGAA) expression therein; however, the analogous AAV2/7 vector achieved much lower efficacy. Administration of the MHCK7-containing vectors significantly increased striated muscle function as assessed by increased Rotarod times at 18 weeks after injection, whereas the CK1-containing vector did not increase Rotarod performance. Importantly, type IIb myofibers in the extensor digitalis longus (EDL) were transduced, thereby correcting a myofiber type that is unresponsive to enzyme replacement therapy. In summary, AAV8 and AAV9-pseudotyped vectors containing the MHCK7 regulatory cassette achieved enhanced efficacy in Pompe disease mice.

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Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

August 2008

Volume

16

Issue

8

Start / End Page

1366 / 1371

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Transduction, Genetic
  • Quadriceps Muscle
  • Promoter Regions, Genetic
  • Myosin Heavy Chains
  • Myocardium
  • Muscle, Striated
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Sun, B., Young, S. P., Li, P., Di, C., Brown, T., Salva, M. Z., … Koeberl, D. D. (2008). Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy. Mol Ther, 16(8), 1366–1371. https://doi.org/10.1038/mt.2008.133
Sun, Baodong, Sarah P. Young, Ping Li, Chunhui Di, Talmage Brown, Maja Z. Salva, Songtao Li, et al. “Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy.Mol Ther 16, no. 8 (August 2008): 1366–71. https://doi.org/10.1038/mt.2008.133.
Sun B, Young SP, Li P, Di C, Brown T, Salva MZ, et al. Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy. Mol Ther. 2008 Aug;16(8):1366–71.
Sun, Baodong, et al. “Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy.Mol Ther, vol. 16, no. 8, Aug. 2008, pp. 1366–71. Pubmed, doi:10.1038/mt.2008.133.
Sun B, Young SP, Li P, Di C, Brown T, Salva MZ, Li S, Bird A, Yan Z, Auten R, Hauschka SD, Koeberl DD. Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy. Mol Ther. 2008 Aug;16(8):1366–1371.

Published In

Mol Ther

DOI

EISSN

1525-0024

Publication Date

August 2008

Volume

16

Issue

8

Start / End Page

1366 / 1371

Location

United States

Related Subject Headings

  • alpha-Glucosidases
  • Transduction, Genetic
  • Quadriceps Muscle
  • Promoter Regions, Genetic
  • Myosin Heavy Chains
  • Myocardium
  • Muscle, Striated
  • Muscle, Skeletal
  • Mice, Knockout
  • Mice