2000 Fiscal Year Final Research Report Summary
Reseach for Gene therapy of ARJP
| Project/Area Number |
11470150
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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 |
Neurology
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| Research Institution | JUNTENDO UNIVERSITY |
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Principal Investigator |
MOCHIZUKI Hideki Juntendo Univ.Dept.of Neurology, Assistant Professor, 医学部, 講師 (90230044)
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| Co-Investigator(Kenkyū-buntansha) |
MIGITA Makoto Nippon Medical Univ, Dept.of Biochemistry, Assistant Professor, 医学部, 講師 (50256963)
HATTORI Nobutaka Juntendo Univ.Dept.of Neurology, Assistant Professor, 医学部, 講師 (80218510)
URABE Takao Juntendo Univ.Dept.of Neurology, Assistant Professor, 医学部, 助手 (60291663)
MIZUNO Yoshikuni Juntendo Univ.Dept.of Neurology, Professor, 医学部, 教授 (30049043)
SHIMADA Takashi Nippon Medical Univ, Dept.of Biochemistry, Professor, 医学部, 教授 (20125074)
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| Project Period (FY) |
1999 – 2000
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| Keywords | ARJP / Parkinson's disease / AAV vector / Parkin gene / Gene therapy |
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| Research Abstract |
In the studies of familiar parkinsonism, the parkin protein has recently been clarified from the analysis of autosomal recessive juvenile parkinsonism (ARJP). ARJP is characterized by selective dopaminergic cell death and the absence of Lewy bodies. Mutations of the parkin gene cause ARJP.
Parkin protein is involved in protein degradation as an ubiquitin-protein ligase collaborating with the ubiquitin-conjugating enzyme UbcH7. A mutant of parkin protein from ARJP patients showed loss of its ubiquitin-protein ligase activity.
Because ARJP involves loss of function, gene therapy using the parkin gene may prevent nigral cell death as a form of anti-apoptotic therapy. Therefore, we established AAV vector system to express Parkin protein for gene therapy in ARJP patients.
The advantages of AAV vector are that it is non-pathogenic, it has stable integration and has the ability to introduce a gene into non-dividing cells. The titer is 108 cfu/ml. Only 5 ul of AAV-GFP was stereotactically injected into the striatum. We got high expression of Parkin protein in the normal mouse striatum. We are going to make knock out mouse for the replacement gene therapy experiment of ARJP.
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