Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors.
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.[1]References
- Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors. Mah, C., Cresawn, K.O., Fraites, T.J., Pacak, C.A., Lewis, M.A., Zolotukhin, I., Byrne, B.J. Gene Ther. (2005) [Pubmed]
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