Correction of glycogen storage disease type II by an adeno-associated virus vector containing a muscle-specific promoter.

Journal Article (Journal Article)

Glycogen storage disease type II (Pompe disease) causes death in infancy from cardiorespiratory failure due to acid alpha-glucosidase (GAA; acid maltase) deficiency. An AAV2 vector pseudotyped as AAV6 (AAV2/6 vector) transiently expressed high-level human GAA in GAA-knockout (GAA-KO) mice without reducing glycogen storage; however, in immunodeficient GAA-KO/SCID mice the AAV2/6 vector expressed high-level GAA and reduced the glycogen content of the injected muscle for 24 weeks. A CD4+/CD8+ lymphocytic infiltrate was observed in response to the AAV2/6 vector in immunocompetent GAA-KO mice. When a muscle-specific creatine kinase promoter was substituted for the CB promoter (AAV-MCKhGAApA), that AAV2/6 vector expressed high-level GAA and reduced glycogen content in immunocompetent GAA-KO mice. Muscle-restricted expression of hGAA provoked only a humoral (not cellular) immune response. Intravenous administration of a high number of particles of AAV-MCKhGAApA as AAV2/7 reduced the glycogen content of the heart and skeletal muscle and corrected individual myofibers in immunocompetent GAA-KO mice 24 weeks postinjection. In summary, persistent correction of muscle glycogen content was achieved with an AAV vector containing a muscle-specific promoter in GAA-KO mice, and this approach should be considered for muscle-targeted gene therapy in Pompe disease.

Full Text

Duke Authors

Cited Authors

  • Sun, B; Zhang, H; Franco, LM; Brown, T; Bird, A; Schneider, A; Koeberl, DD

Published Date

  • June 2005

Published In

Volume / Issue

  • 11 / 6

Start / End Page

  • 889 - 898

PubMed ID

  • 15922959

International Standard Serial Number (ISSN)

  • 1525-0016

Digital Object Identifier (DOI)

  • 10.1016/j.ymthe.2005.01.012


  • eng

Conference Location

  • United States