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Long-term efficacy after [E1-, polymerase-] adenovirus-mediated transfer of human acid-alpha-glucosidase gene into glycogen storage disease type II knockout mice.
Hum Gene Ther. 2001 May 20; 12(8):955-65.HG

Abstract

Glycogen storage disease type II (GSD-II) is a lethal, autosomal recessive metabolic myopathy caused by a lack of acid-alpha-glucosidase (GAA) activity in the cardiac and skeletal muscles. Absence of adequate intralysosomal GAA activity results in massive amounts of glycogen accumulation in multiple muscle groups, resulting in morbidity and mortality secondary to respiratory embarrassment and/or cardiomyopathy. In a mouse model of GSD-II, we demonstrate that infection of the murine liver with a modified adenovirus (Ad) vector encoding human GAA (hGAA) resulted in long-term persistence of the vector in liver tissues for at least 6 months. Despite both a rapid shutdown of hGAA mRNA expression from the vector, as well as the elicitation of anti-hGAA antibody responses (hGAA is a foreign antigen in this model), the hGAA secreted by the liver was taken up by all muscle groups analyzed and, remarkably, persisted in them for at least 6 months. The persistence of the protein also correlated with long-term correction of pathologic intramuscular glycogen accumulations in all muscle groups tested, but most notably the cardiac tissues, which demonstrated a significantly decreased glycogen content for at least 190 days after a single vector injection. The results suggest that gene therapy strategies may have the potential to significantly improve the clinical course for GSD-II patients.

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 available

Pub Type(s)

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

Language

eng

PubMed ID

11387060

Citation

Ding, E Y., et al. "Long-term Efficacy After [E1-, Polymerase-] Adenovirus-mediated Transfer of Human Acid-alpha-glucosidase Gene Into Glycogen Storage Disease Type II Knockout Mice." Human Gene Therapy, vol. 12, no. 8, 2001, pp. 955-65.
Ding EY, Hodges BL, Hu H, et al. Long-term efficacy after [E1-, polymerase-] adenovirus-mediated transfer of human acid-alpha-glucosidase gene into glycogen storage disease type II knockout mice. Hum Gene Ther. 2001;12(8):955-65.
Ding, E. Y., Hodges, B. L., Hu, H., McVie-Wylie, A. J., Serra, D., Migone, F. K., Pressley, D., Chen, Y. T., & Amalfitano, A. (2001). Long-term efficacy after [E1-, polymerase-] adenovirus-mediated transfer of human acid-alpha-glucosidase gene into glycogen storage disease type II knockout mice. Human Gene Therapy, 12(8), 955-65.
Ding EY, et al. Long-term Efficacy After [E1-, Polymerase-] Adenovirus-mediated Transfer of Human Acid-alpha-glucosidase Gene Into Glycogen Storage Disease Type II Knockout Mice. Hum Gene Ther. 2001 May 20;12(8):955-65. PubMed PMID: 11387060.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Long-term efficacy after [E1-, polymerase-] adenovirus-mediated transfer of human acid-alpha-glucosidase gene into glycogen storage disease type II knockout mice. AU - Ding,E Y, AU - Hodges,B L, AU - Hu,H, AU - McVie-Wylie,A J, AU - Serra,D, AU - Migone,F K, AU - Pressley,D, AU - Chen,Y T, AU - Amalfitano,A, PY - 2001/6/2/pubmed PY - 2001/8/24/medline PY - 2001/6/2/entrez SP - 955 EP - 65 JF - Human gene therapy JO - Hum. Gene Ther. VL - 12 IS - 8 N2 - Glycogen storage disease type II (GSD-II) is a lethal, autosomal recessive metabolic myopathy caused by a lack of acid-alpha-glucosidase (GAA) activity in the cardiac and skeletal muscles. Absence of adequate intralysosomal GAA activity results in massive amounts of glycogen accumulation in multiple muscle groups, resulting in morbidity and mortality secondary to respiratory embarrassment and/or cardiomyopathy. In a mouse model of GSD-II, we demonstrate that infection of the murine liver with a modified adenovirus (Ad) vector encoding human GAA (hGAA) resulted in long-term persistence of the vector in liver tissues for at least 6 months. Despite both a rapid shutdown of hGAA mRNA expression from the vector, as well as the elicitation of anti-hGAA antibody responses (hGAA is a foreign antigen in this model), the hGAA secreted by the liver was taken up by all muscle groups analyzed and, remarkably, persisted in them for at least 6 months. The persistence of the protein also correlated with long-term correction of pathologic intramuscular glycogen accumulations in all muscle groups tested, but most notably the cardiac tissues, which demonstrated a significantly decreased glycogen content for at least 190 days after a single vector injection. The results suggest that gene therapy strategies may have the potential to significantly improve the clinical course for GSD-II patients. SN - 1043-0342 UR - https://www.unboundmedicine.com/medline/citation/11387060/Long_term_efficacy_after_[E1__polymerase_]_adenovirus_mediated_transfer_of_human_acid_alpha_glucosidase_gene_into_glycogen_storage_disease_type_II_knockout_mice_ L2 - https://www.liebertpub.com/doi/full/10.1089/104303401750195917?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -