2000 Fiscal Year Final Research Report Summary
Gene therapy for Krabbe disease with microglial cells derived from brain
| Project/Area Number |
11670792
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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 | The Jikei University School of Medicine |
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Principal Investigator |
GOMIBUCHI Ichizou Jikei Univ., Dept.of Pediatrics senior investigator, 医学部, 助手 (50205621)
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| Co-Investigator(Kenkyū-buntansha) |
岩澤 京子 東京慈恵会医科大学, 医学部, 助手 (10301524)
OHASHI Touya Jikei Univ., Dept.of Pediatrics assi prof., 医学部, 講師 (60160595)
ETO Yoshikarsu Jikei Univ., Dept.of Pediatrics prof., 医学部, 教授 (50056909)
KOBAYASHI Hiroshi Jikei Univ., Dept.of Pediatrics senior investigator, 医学部, 助手 (90266619)
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| Project Period (FY) |
1999 – 2000
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| Keywords | gene therapy / mutation / lysosomal disorder / アデノウイルスベクター |
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| Research Abstract |
The some disorders caused by enzyme deficiency manifest the neurological symptoms. Particularly lysosomal and urea cycle disorders show central nervous signs. Hyperornithinemia-hyperammonemia-homocitrullinuria (H.H.H.) syndrome is caused by genetic defect of ORTN1 gene. To clarify the molecular mechanism in H.H.H.syndrome we investigated mutation analysis of ORTN1 gene from Japanese patients. Three novel mutations (G27E, insAAC and R179X) were identified in Japanese patients with H.H.H.syndrome. This abnormality may cause the insufficiency of transport of ornithine. Since other aim of our project is to overcome the low transduction efficacy of gene transfer to human stem cells, we studied the usefulness of macrophages as target cells for lysosomal disorders. A retroviral vector expressing human beta-glucuronidase (HBG) was used to infect macrophages cultivated from Sly mouse. After transplantation, HBG positive cells were observed histochemically and pathologic in Japanese patients with type 1 Gaucher disease and sustained administration of full doses in patients at greater risk of important skeletal complications were clarified by our studies. Our findings underline the importance of comprehensive genotyping, long-term follow-up and careful neurologicalexamination in patients with early-onset GD.Long-term high dose enzyme replacement therapy may be required to obtain sufficient improvement to maintain health among patients with severe GD.
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