| Project/Area Number |
14370253
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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 | Nippon Medical School |
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Principal Investigator |
SHIMADA Takashi Nippon Medical School, Professor, 大学院・医学研究科, 教授 (20125074)
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| Co-Investigator(Kenkyū-buntansha) |
MIGITA Makoto Nippon Medical School, Associate professor, 医学部, 助教授 (50256963)
MIYAKE Koichi Nippon Medical School, Assistant professor, 医学部, 講師 (90267211)
MODHIZUKI Hideki Juntendo University, Associate professor, 医学部, 講師 (90230044)
NISHI Katsunori Tokyo Metropolitan Inst for Neuroscience, Dept Neurology, Director, 副参事研究員 (00138257)
平井 幸彦 日本医科大学, 医学部, 講師 (10089617)
鈴木 聡 日本医科大学, 医学部, 助手 (70246940)
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| Project Period (FY) |
2002 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,000,000 (Direct Cost: ¥14,000,000)
Fiscal Year 2004: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | gene therapy / cell therapy / lysosomal disorders / stem cells / neural stem cells / AAV vector / 異染性ロイコジストロフィー / アリルサルファターゼ / 多能性幹細胞 / 脂肪組織由来幹細胞 / HIVベクター / 異染性白質ジストロフィー / 多能性骨髄幹細胞 |
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| Research Abstract |
1.Gene therapy : We examined the utility of recently identified sulfatase activating enzyme (FGE) for expression of arylsulfatase A(ASA) in gene therapy of metachromatic leukodustrophy(MLD). Our data demonstrated that FGE co-expression is essential for synthesis and secretion of functional ASA both in vitro and in vivo. In a therapeutic model experiment, we generated AAV1 vector carrying either ASA or FGE cDNA. Simultaneous injection of these vectors into the hippocampus of MLD mice significantly increased ASA activity and decreased sulfatide accumulation in the wide areas of the brain. Significant improvement of behavior was confirmed by the rotarod test and the walking pattern. These result support that FGE co-expression is essential for efficient synthesis of functional ASA and have significant implications for the development of MLD gene therapy.
2.Stem cell therapy : Using chimeric mice stably reconstituted with bone marrow cells from GFP transgenic mice, we demonstrated that mesenchymal stem cells derived from bone marrow (BSC) could differentiate various cell lineages. We also succeeded in preparing pluripotent stem cells from adipose tissues(ASC). The feasibility of cell therapy of MLD was demonstrate by direct inoculation of neural progenitor cells stably tranduced with lentiviral vector carrying ASA cDNA. Genetically engineered stem cells may be useful for therapy for neurodegenerative disorders.
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