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Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy.
Mol Ther. 2008 Aug; 16(8):1366-71.MT

Abstract

Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the deficiency of acid alpha-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. An adeno-associated virus 2/8 (AAV2/8) vector containing the muscle creatine kinase (MCK) (CK1) reduced glycogen content by approximately 50% in the heart and quadriceps in GAA-knockout (GAA-KO) mice; furthermore, an AAV2/8 vector containing the hybrid alpha-myosin heavy chain enhancer-/MCK enhancer-promoter (MHCK7) cassette reduced glycogen content by >95% in heart and >75% in the diaphragm and quadriceps. Transduction with an AAV2/8 vector was higher in the quadriceps than in the gastrocnemius. An AAV2/9 vector containing the MHCK7 cassette corrected GAA deficiency in the distal hindlimb, and glycogen accumulations were substantially cleared by human GAA (hGAA) expression therein; however, the analogous AAV2/7 vector achieved much lower efficacy. Administration of the MHCK7-containing vectors significantly increased striated muscle function as assessed by increased Rotarod times at 18 weeks after injection, whereas the CK1-containing vector did not increase Rotarod performance. Importantly, type IIb myofibers in the extensor digitalis longus (EDL) were transduced, thereby correcting a myofiber type that is unresponsive to enzyme replacement therapy. In summary, AAV8 and AAV9-pseudotyped vectors containing the MHCK7 regulatory cassette achieved enhanced efficacy in Pompe disease mice.

Authors+Show Affiliations

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo 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

Language

eng

PubMed ID

18560415

Citation

Sun, Baodong, et al. "Correction of Multiple Striated Muscles in Murine Pompe Disease Through Adeno-associated Virus-mediated Gene Therapy." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 16, no. 8, 2008, pp. 1366-71.
Sun B, Young SP, Li P, et al. Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy. Mol Ther. 2008;16(8):1366-71.
Sun, B., Young, S. P., Li, P., Di, C., Brown, T., Salva, M. Z., Li, S., Bird, A., Yan, Z., Auten, R., Hauschka, S. D., & Koeberl, D. D. (2008). Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy. Molecular Therapy : the Journal of the American Society of Gene Therapy, 16(8), 1366-71. https://doi.org/10.1038/mt.2008.133
Sun B, et al. Correction of Multiple Striated Muscles in Murine Pompe Disease Through Adeno-associated Virus-mediated Gene Therapy. Mol Ther. 2008;16(8):1366-71. PubMed PMID: 18560415.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correction of multiple striated muscles in murine Pompe disease through adeno-associated virus-mediated gene therapy. AU - Sun,Baodong, AU - Young,Sarah P, AU - Li,Ping, AU - Di,Chunhui, AU - Brown,Talmage, AU - Salva,Maja Z, AU - Li,Songtao, AU - Bird,Andrew, AU - Yan,Zhen, AU - Auten,Richard, AU - Hauschka,Stephen D, AU - Koeberl,Dwight D, Y1 - 2008/06/17/ PY - 2008/6/19/pubmed PY - 2009/1/23/medline PY - 2008/6/19/entrez SP - 1366 EP - 71 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 16 IS - 8 N2 - Glycogen storage disease type II (Pompe disease; MIM 232300) stems from the deficiency of acid alpha-glucosidase (GAA; acid maltase; EC 3.2.1.20), which primarily involves cardiac and skeletal muscles. An adeno-associated virus 2/8 (AAV2/8) vector containing the muscle creatine kinase (MCK) (CK1) reduced glycogen content by approximately 50% in the heart and quadriceps in GAA-knockout (GAA-KO) mice; furthermore, an AAV2/8 vector containing the hybrid alpha-myosin heavy chain enhancer-/MCK enhancer-promoter (MHCK7) cassette reduced glycogen content by >95% in heart and >75% in the diaphragm and quadriceps. Transduction with an AAV2/8 vector was higher in the quadriceps than in the gastrocnemius. An AAV2/9 vector containing the MHCK7 cassette corrected GAA deficiency in the distal hindlimb, and glycogen accumulations were substantially cleared by human GAA (hGAA) expression therein; however, the analogous AAV2/7 vector achieved much lower efficacy. Administration of the MHCK7-containing vectors significantly increased striated muscle function as assessed by increased Rotarod times at 18 weeks after injection, whereas the CK1-containing vector did not increase Rotarod performance. Importantly, type IIb myofibers in the extensor digitalis longus (EDL) were transduced, thereby correcting a myofiber type that is unresponsive to enzyme replacement therapy. In summary, AAV8 and AAV9-pseudotyped vectors containing the MHCK7 regulatory cassette achieved enhanced efficacy in Pompe disease mice. SN - 1525-0024 UR - https://www.unboundmedicine.com/medline/citation/18560415/Correction_of_multiple_striated_muscles_in_murine_Pompe_disease_through_adeno_associated_virus_mediated_gene_therapy_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(16)32270-5 DB - PRIME DP - Unbound Medicine ER -