• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Fundamental Reseach on Gene Therapy for Mitochondrial Gemone Disorders

Research Project

Project/Area Number 09670811
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pediatrics
Research InstitutionUniversity of Tokushima

Principal Investigator

SAIJO Takahiko  University of Tokushima Medical School Hospital Research Associate, 医学部附属病院, 助手 (10284291)

Co-Investigator(Kenkyū-buntansha) KURODA Yasuhiro  University of Tokushima, School of Medicine, Professor, 医学部, 教授 (20035471)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1998: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1997: ¥2,700,000 (Direct Cost: ¥2,700,000)
KeywordsMitochondria / Gene Therapy / Mitochondrial Genome / Leigh's syndrome / Leighの脳症
Research Abstract

Defects of the mitochondrial genome are increasingly being recognized as important causes of neuromuscular disease, such as fatal lactic acidosis in infancy and muscle disease in adults. For most patients there is no satisfactory treatment and there is a gradual deterioration leading to severe disability and death. In the absence of any biochemical treatment, gene therapy must be considered for these patients.
In order to probe the possibility of the gene therapy for the mitochondrial genome disorders, we choose Leigh's syndrome as a model. Many cases of Leigh's syndrome are caused by a point mutation at nucleotide 8993 of ATPase 6 subunit. We introduced a modified ATPase 6 gene into the nucleus of the lymphoblastoid cell lines from the patients with Leigh's syndrome. The introduced gene was modified so that by adding a DNA sequence encoding the leader peptide of E1alpha subunit of pyruvate dehydrogenasc complex the product protein is imported into the mitochondria and that the protein has the correct amino acid sequence when translated based upon nuclear codon usage. The product protein was successfully transported into mitochondria and the leader peptide was cleaved, leaving a protein which could be identical to ATPase 6 subunit. When the modified ATPase 6 gene was introduced into the lymphoblastoid cells from thc patients with Leigh's syndrome, ATP systhesis was increase to a level comparable to level s of the patients, who are asymptomatic. This finding strongly suggested that in some mitochondrial genome disorders, gene therapy is possible by introducing a gene into the nucleus, not in the mitocondria.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (6 results)

All Other

All Publications (6 results)

  • [Publications] Takahiko Saijo: "Stable restoration of pyruvate dehydrogenase complex in E1-defective human lymphoblastoid cells" Biochemical and Biophysical Research Communications. 228. 446-451 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Etsuo Naito: "Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamine-responsive PDH deficiency" Journal of Inherited Metabolic Disease. 20. 539-548 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Saijo, T., et al: "Stable restoration of pyruvate dehydrogenase complex in E1-defective human lymphoblastoid cells : evidence that three C-terminall amino acids of E1alpha are essential for the structural integrity of heterotetrameric E1.^<tic islets>" Biochemical and Biophysical Research Communications. 228. 446-451 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Naito, E., et al: "Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamin-responsive pyruvate dehydrogenase deficiency." Journal of Inherited Metabolic Disease. 20. 539-548 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Takahiko SaiJo: "Stable restoration of pyrurate deehydrogenase complex in E1-defective human lymphoblastold cells" Biochemical and Biophysical research Communications. 228. 446-451 (1996)

    • Related Report
      1998 Annual Research Report
  • [Publications] Etsuo Naito: "Biochemical and molecular analysis of an X-linked case of Leigh syndrome associated with thiamine-responsive PDHde deficiensy" Jaurnal of Inherited metablic,disease. 20. 539-548 (1997)

    • Related Report
      1998 Annual Research Report

URL: 

Published: 1997-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi