Tags

Type your tag names separated by a space and hit enter

Adeno-associated virus-mediated transfer of human acid maltase gene results in a transient reduction of glycogen accumulation in muscle of Japanese quail with acid maltase deficiency.
Gene Ther 2002; 9(9):554-63GT

Abstract

Glycogen storage disease type II (GSD II), Pompe's disease, is caused by the deficiency of acid alpha-D-glucosidase (GAA) in lysosome and is the most common form of GSD in Taiwan. Most cases are the infantile form. The disease is relentless and most patients die of cardiac failure and respiratory tract infection in the first year of life. At present, no treatment has been proved effective for this fatal disease. The applicability of enzyme replacement therapy is under investigation. However, high price and transient efficiency are the major problems to be solved. Accordingly, gene therapy by viral method has been conducted. In this study we constructed a plasmid that contained 5'-shortened BglII-NotI fragment human GAA cDNA, downstream of CMV promoter and bovine growth hormone polyadenylation signal, as well as AAV ITR region. When fibroblasts obtained from GSD II patients were cultured and infected with rAAV-GAA, the GAA activity of the fibroblasts increased four- to five-fold. Using acid maltase deficient (AMD) Japanese quail as the animal model, rcAAV-GAA 0.1 ml per site (1 x 10(9)-10) particles), totally 10 different sites to make 1 ml (1 x 10(1)0-11) particles), was injected into unilateral deep pectoral muscle of AMD quails. Medium (hepes) was only injected in the same way into the contralateral deep pectoral muscle to serve as control. Four days after injection, PAS staining showed disappearance of the glycogenosomes with regeneration of myocytes surrounding the intramuscular injected area as compared with the contralateral muscle of the same birds. Using anti-GAA monoclonal antibody, GAA was demonstrated on the regenerated myocytes by immunohistochemical staining and absent on the contralateral muscle of the same birds. Nevertheless, T lymphocytes infiltration was noted in both the rcAAV-GAA and hepes (medium) injected muscles and more prominent in the rcAAV-GAA-injected site. Functional evaluation demonstrated that wing flapping movement improved with wide flapping in the rAAV-GAA injected side, but not in the counterpart. Unfortunately, these histochemical and functional improvements faded away in 14 days, probably due to destruction of rcAAV by cell-mediated immunity of infiltrated T cells. Taken together, the present study suggests that rAAV can enter either human or quail cells and express and effectively reduce the glycogen accumulation in the skeletal muscle of AMD quails. These preliminary results are similar to these of low-dose rGAA replacement therapy. The mechanisms underlying the induction of cell-mediated immunity are unknown. How to elevate the number of packaged AAV, enhance the infectivity of AAV and reduce cell-mediated immunity must be solved in the future.

Authors+Show Affiliations

Department of Pediatrics, Taipei Veterans General Hospital, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

11973631

Citation

Lin, C-Y, et al. "Adeno-associated Virus-mediated Transfer of Human Acid Maltase Gene Results in a Transient Reduction of Glycogen Accumulation in Muscle of Japanese Quail With Acid Maltase Deficiency." Gene Therapy, vol. 9, no. 9, 2002, pp. 554-63.
Lin CY, Ho CH, Hsieh YH, et al. Adeno-associated virus-mediated transfer of human acid maltase gene results in a transient reduction of glycogen accumulation in muscle of Japanese quail with acid maltase deficiency. Gene Ther. 2002;9(9):554-63.
Lin, C. Y., Ho, C. H., Hsieh, Y. H., & Kikuchi, T. (2002). Adeno-associated virus-mediated transfer of human acid maltase gene results in a transient reduction of glycogen accumulation in muscle of Japanese quail with acid maltase deficiency. Gene Therapy, 9(9), pp. 554-63.
Lin CY, et al. Adeno-associated Virus-mediated Transfer of Human Acid Maltase Gene Results in a Transient Reduction of Glycogen Accumulation in Muscle of Japanese Quail With Acid Maltase Deficiency. Gene Ther. 2002;9(9):554-63. PubMed PMID: 11973631.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adeno-associated virus-mediated transfer of human acid maltase gene results in a transient reduction of glycogen accumulation in muscle of Japanese quail with acid maltase deficiency. AU - Lin,C-Y, AU - Ho,C-H, AU - Hsieh,Y-H, AU - Kikuchi,T, PY - 2001/01/18/received PY - 2001/12/15/accepted PY - 2002/4/26/pubmed PY - 2002/5/15/medline PY - 2002/4/26/entrez SP - 554 EP - 63 JF - Gene therapy JO - Gene Ther. VL - 9 IS - 9 N2 - Glycogen storage disease type II (GSD II), Pompe's disease, is caused by the deficiency of acid alpha-D-glucosidase (GAA) in lysosome and is the most common form of GSD in Taiwan. Most cases are the infantile form. The disease is relentless and most patients die of cardiac failure and respiratory tract infection in the first year of life. At present, no treatment has been proved effective for this fatal disease. The applicability of enzyme replacement therapy is under investigation. However, high price and transient efficiency are the major problems to be solved. Accordingly, gene therapy by viral method has been conducted. In this study we constructed a plasmid that contained 5'-shortened BglII-NotI fragment human GAA cDNA, downstream of CMV promoter and bovine growth hormone polyadenylation signal, as well as AAV ITR region. When fibroblasts obtained from GSD II patients were cultured and infected with rAAV-GAA, the GAA activity of the fibroblasts increased four- to five-fold. Using acid maltase deficient (AMD) Japanese quail as the animal model, rcAAV-GAA 0.1 ml per site (1 x 10(9)-10) particles), totally 10 different sites to make 1 ml (1 x 10(1)0-11) particles), was injected into unilateral deep pectoral muscle of AMD quails. Medium (hepes) was only injected in the same way into the contralateral deep pectoral muscle to serve as control. Four days after injection, PAS staining showed disappearance of the glycogenosomes with regeneration of myocytes surrounding the intramuscular injected area as compared with the contralateral muscle of the same birds. Using anti-GAA monoclonal antibody, GAA was demonstrated on the regenerated myocytes by immunohistochemical staining and absent on the contralateral muscle of the same birds. Nevertheless, T lymphocytes infiltration was noted in both the rcAAV-GAA and hepes (medium) injected muscles and more prominent in the rcAAV-GAA-injected site. Functional evaluation demonstrated that wing flapping movement improved with wide flapping in the rAAV-GAA injected side, but not in the counterpart. Unfortunately, these histochemical and functional improvements faded away in 14 days, probably due to destruction of rcAAV by cell-mediated immunity of infiltrated T cells. Taken together, the present study suggests that rAAV can enter either human or quail cells and express and effectively reduce the glycogen accumulation in the skeletal muscle of AMD quails. These preliminary results are similar to these of low-dose rGAA replacement therapy. The mechanisms underlying the induction of cell-mediated immunity are unknown. How to elevate the number of packaged AAV, enhance the infectivity of AAV and reduce cell-mediated immunity must be solved in the future. SN - 0969-7128 UR - https://www.unboundmedicine.com/medline/citation/11973631/Adeno_associated_virus_mediated_transfer_of_human_acid_maltase_gene_results_in_a_transient_reduction_of_glycogen_accumulation_in_muscle_of_Japanese_quail_with_acid_maltase_deficiency_ L2 - http://dx.doi.org/10.1038/sj.gt.3301672 DB - PRIME DP - Unbound Medicine ER -