1998 Fiscal Year Final Research Report Summary
Fundamental Reseach on Gene Therapy for Mitochondrial Gemone Disorders
| Project/Area Number |
09670811
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | University of Tokushima |
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Principal Investigator |
SAIJO Takahiko University of Tokushima Medical School Hospital Research Associate, 医学部附属病院, 助手 (10284291)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Yasuhiro University of Tokushima, School of Medicine, Professor, 医学部, 教授 (20035471)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Mitochondria / Gene Therapy / Mitochondrial Genome / Leigh's syndrome |
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| 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.
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Research Products
(4 results)
