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

C. Mah, K. O. Cresawn, T. J. Fraites, C. A. Pacak, M. A. Lewis, I. Zolotukhin, B. J. Byrne

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63 Scopus citations


Glycogen storage disease type II (GSDII) is caused by a lack of functional lysosomal acid α-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±090% 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.

Original languageEnglish (US)
Pages (from-to)1405-1409
Number of pages5
JournalGene therapy
Issue number18
StatePublished - Sep 2005
Externally publishedYes

Bibliographical note

Funding Information:
We gratefully acknowledge the University of Florida Powell Gene Therapy Center Vector Core Laboratory, which produced some of the rAAV vectors used in this study. This work was supported by grants from the National Institutes of Health (NHLBI P01 HL59412, NIDDK P01 DK58327), the Muscular Dystrophy Association, and the American Heart Association Florida and Puerto Rico Affiliate (KOC, TJF, CAP) and National Center (CM). BJB, The Johns Hopkins University, and the University of Florida could be entitled to patent royalties for inventions described in this manuscript.


  • Acid alpha-glucosidase
  • Adeno-associated virus
  • Gene delivery
  • Glycogen storage disease type II
  • Pompe


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