1998 Fiscal Year Final Research Report Summary
Studies of inherited neurodegenerative disease ; mutation analysis and gene therapy
| Project/Area Number |
09470186
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | The Jikei University School of Medicine |
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Principal Investigator |
MAEKAWA K. Jikei Univ., Dept.of Pediatrics prof., 医学部・小児科, 教授 (80056613)
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| Co-Investigator(Kenkyū-buntansha) |
OHASHI T. Jikei Univ., Dept.of Pediatrics assi.prof., 医学部・小児科, 講師 (60160595)
KAWAME H. Jikei Univ., Dept.of Pediatrics senior investigator, 医学部・小児科, 助手 (60246395)
IDA H. Jikei Univ., Dept.of Pediatrics assi.prof., 医学部・小児科, 講師 (90167255)
MATSUSHIMA H. Jikei Univ., Dept.of Pediatrics asso.prof., 医学部・小児科, 助教授 (70190460)
ETO Y. Jikei Univ., Dept.of Pediatrics prof., 医学部・小児科, 教授 (50056909)
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| Project Period (FY) |
1997 – 1998
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| Keywords | Inborn errors of metabolism / Gene Tharapy / Adenovirus / Retrovirus / Gene mutation / Animal model |
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| Research Abstract |
We investigated the mutation analysis and gene therapy for neurodegenerative disorders caused by enzyme defect. We identified and genotyped a patient with neuronopathic Gaucher disease (GD) presenting unique phenotype, hydrocephalus, valvur calcification and corneal opacities. This patient was homozygous for D409H mutation. We performed pathological examinations of a patient with type 2 GD treated with enzyme replacement therapy. This study suggest that gene therapy using neurotropic vector should be required for treating type 2 GD.We produced recombinant adenovirus that express human glucuronidase and this recombinant adenovirus to animal model intravenously. Pathological abnormalities in liver and spleen were improved, and the urinary glycosaminoglycans were also reduced in treated mice. Transduction of enzyme into brain was seen only by adminstration of direct injection of recombinant adenovirus into the lateral ventricles. We succeeded in efficient transferring glucuronidase gene in a retroviral vector to human hematopoietic progenitor cells. These data provide encouragement that gene therapy for neurodegenerative disorders caused by enzyme defect is efficacious.
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