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Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II.
Mol Ther. 2005 Nov; 12(5):876-84.MT

Abstract

Glycogen storage disease type II (GSD-II; Pompe disease) is caused by a deficiency of acid alpha-glucosidase (GAA; acid maltase) and manifests as muscle weakness, hypertrophic cardiomyopathy, and respiratory failure. Adeno-associated virus vectors containing either a liver-specific promoter (LSP) (AAV-LSPhGAApA) or a hybrid CB promoter (AAV-CBhGAApA) to drive human GAA expression were pseudotyped as AAV8 and administered to immunocompetent GAA-knockout mice. Secreted hGAA was detectable in plasma between 1 day and 12 weeks postadministration with AAV-LSPhGAApA and only from 1 to 8 days postadministration for AAV-CBGAApA. No anti-GAA antibodies were detected in response to AAV-LSPhGAApA (<1:200), whereas AAV-CBhGAApA provoked an escalating antibody response starting 2 weeks postadministration. The LSP drove approximately 60-fold higher GAA expression than the CB promoter in the liver by 12 weeks following vector administration. Furthermore, the detected cellular immunity was provoked by AAV-CBhGAApA, as detected by ELISpot and CD4+/CD8+ lymphocyte immunodetection. GAA activity was increased to higher than normal and glycogen content was reduced to essentially normal levels in the heart and skeletal muscle following administration of AAV-LSPhGAApA. Therefore, liver-restricted GAA expression with an AAV vector evaded immunity and enhanced efficacy in GSD-II mice.

Authors+Show Affiliations

Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Durham, NC 27710, 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

16005263

Citation

Franco, Luis M., et al. "Evasion of Immune Responses to Introduced Human Acid Alpha-glucosidase By Liver-restricted Expression in Glycogen Storage Disease Type II." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 12, no. 5, 2005, pp. 876-84.
Franco LM, Sun B, Yang X, et al. Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II. Mol Ther. 2005;12(5):876-84.
Franco, L. M., Sun, B., Yang, X., Bird, A., Zhang, H., Schneider, A., Brown, T., Young, S. P., Clay, T. M., Amalfitano, A., Chen, Y. T., & Koeberl, D. D. (2005). Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II. Molecular Therapy : the Journal of the American Society of Gene Therapy, 12(5), 876-84.
Franco LM, et al. Evasion of Immune Responses to Introduced Human Acid Alpha-glucosidase By Liver-restricted Expression in Glycogen Storage Disease Type II. Mol Ther. 2005;12(5):876-84. PubMed PMID: 16005263.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Evasion of immune responses to introduced human acid alpha-glucosidase by liver-restricted expression in glycogen storage disease type II. AU - Franco,Luis M, AU - Sun,Baodong, AU - Yang,Xiaoyi, AU - Bird,Andrew, AU - Zhang,Haoyue, AU - Schneider,Ayn, AU - Brown,Talmage, AU - Young,Sarah P, AU - Clay,Timothy M, AU - Amalfitano,Andrea, AU - Chen,Y T, AU - Koeberl,Dwight D, Y1 - 2005/07/06/ PY - 2004/10/01/received PY - 2005/04/28/revised PY - 2005/04/28/accepted PY - 2005/7/12/pubmed PY - 2006/1/7/medline PY - 2005/7/12/entrez SP - 876 EP - 84 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 12 IS - 5 N2 - Glycogen storage disease type II (GSD-II; Pompe disease) is caused by a deficiency of acid alpha-glucosidase (GAA; acid maltase) and manifests as muscle weakness, hypertrophic cardiomyopathy, and respiratory failure. Adeno-associated virus vectors containing either a liver-specific promoter (LSP) (AAV-LSPhGAApA) or a hybrid CB promoter (AAV-CBhGAApA) to drive human GAA expression were pseudotyped as AAV8 and administered to immunocompetent GAA-knockout mice. Secreted hGAA was detectable in plasma between 1 day and 12 weeks postadministration with AAV-LSPhGAApA and only from 1 to 8 days postadministration for AAV-CBGAApA. No anti-GAA antibodies were detected in response to AAV-LSPhGAApA (<1:200), whereas AAV-CBhGAApA provoked an escalating antibody response starting 2 weeks postadministration. The LSP drove approximately 60-fold higher GAA expression than the CB promoter in the liver by 12 weeks following vector administration. Furthermore, the detected cellular immunity was provoked by AAV-CBhGAApA, as detected by ELISpot and CD4+/CD8+ lymphocyte immunodetection. GAA activity was increased to higher than normal and glycogen content was reduced to essentially normal levels in the heart and skeletal muscle following administration of AAV-LSPhGAApA. Therefore, liver-restricted GAA expression with an AAV vector evaded immunity and enhanced efficacy in GSD-II mice. SN - 1525-0016 UR - https://www.unboundmedicine.com/medline/citation/16005263/Evasion_of_immune_responses_to_introduced_human_acid_alpha_glucosidase_by_liver_restricted_expression_in_glycogen_storage_disease_type_II_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(05)00231-5 DB - PRIME DP - Unbound Medicine ER -