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Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors.
Gene Ther. 2005 Sep; 12(18):1405-9.GT

Abstract

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.

Authors+Show Affiliations

Powell Gene Therapy Center, University of Florida College of Medicine, Gainesville, FL 32610-0296, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

15920463

Citation

Mah, C, et al. "Sustained Correction of Glycogen Storage Disease Type II Using Adeno-associated Virus Serotype 1 Vectors." Gene Therapy, vol. 12, no. 18, 2005, pp. 1405-9.
Mah C, Cresawn KO, Fraites TJ, et al. Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors. Gene Ther. 2005;12(18):1405-9.
Mah, C., Cresawn, K. O., Fraites, T. J., Pacak, C. A., Lewis, M. A., Zolotukhin, I., & Byrne, B. J. (2005). Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors. Gene Therapy, 12(18), 1405-9.
Mah C, et al. Sustained Correction of Glycogen Storage Disease Type II Using Adeno-associated Virus Serotype 1 Vectors. Gene Ther. 2005;12(18):1405-9. PubMed PMID: 15920463.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sustained correction of glycogen storage disease type II using adeno-associated virus serotype 1 vectors. AU - Mah,C, AU - Cresawn,K O, AU - Fraites,T J,Jr AU - Pacak,C A, AU - Lewis,M A, AU - Zolotukhin,I, AU - Byrne,B J, PY - 2005/5/28/pubmed PY - 2006/1/18/medline PY - 2005/5/28/entrez SP - 1405 EP - 9 JF - Gene therapy JO - Gene Ther. VL - 12 IS - 18 N2 - 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. SN - 0969-7128 UR - https://www.unboundmedicine.com/medline/citation/15920463/Sustained_correction_of_glycogen_storage_disease_type_II_using_adeno_associated_virus_serotype_1_vectors_ L2 - http://dx.doi.org/10.1038/sj.gt.3302550 DB - PRIME DP - Unbound Medicine ER -