Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors

Gene Ther. 2005 Sep;12(18):1405-9. doi: 10.1038/


Glycogen storage disease type II (GSDII) is caused by a lack of functional lysosomal acid alpha-glucosidase (GAA). Affected individuals store glycogen in lysosomes beginning during gestation, ultimately resulting in fatal hypertrophic cardiomyopathy and respiratory failure. We have assessed the utility of recombinant adeno-associated virus (rAAV) vectors to restore GAA activity in vivo in a mouse model of GSDII (Gaa(-/-)). A single systemic administration of a rAAV serotype 1 (rAAV1) vector to neonate animals resulted in restored cardiac GAA activity to 6.4 times the normal level (mean=641+/-190% of normal (Gaa(+/+)) levels with concomitant glycogen clearance) at 11 months postinjection. Greater than 20% of normal levels of GAA activity were also observed in the diaphragm and quadriceps muscles. Furthermore, functional correction of the soleus skeletal muscle was also observed compared to age-matched untreated Gaa(-/-) control animals. These results demonstrate that rAAV1 vectors can mediate sustained therapeutic levels of correction of both skeletal and cardiac muscles in a model of fatal cardiomyopathy and muscular dystrophy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dependovirus / genetics*
  • Diaphragm / enzymology
  • Disease Models, Animal
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage*
  • Glucan 1,4-alpha-Glucosidase / genetics*
  • Glucan 1,4-alpha-Glucosidase / metabolism
  • Glycogen Storage Disease Type II / enzymology
  • Glycogen Storage Disease Type II / therapy*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Skeletal / enzymology
  • Myocardium / enzymology
  • Transduction, Genetic / methods*
  • alpha-Glucosidases


  • alpha-Glucosidases
  • Glucan 1,4-alpha-Glucosidase