Drug Development for GM1 Gangliosidosis using the patients-derived iPS cells
| Project/Area Number |
16K19654
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Pediatrics
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| Research Institution | Kumamoto University |
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Principal Investigator |
Kajihara Ryutaro 熊本大学, 大学院生命科学研究部(保), 助教 (00738221)
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| Research Collaborator |
ERA Takumi 熊本大学, 発生医学研究所, 教授 (00273706)
NUMAKAWA Tadahiro 熊本大学, 発生医学研究所, 特定事業研究員 (40425690)
ENDO Fumio 熊本大学, 大学院生命科学研究部, 教授 (00176801)
MASTUMOTO Shirou 熊本大学, 医学部附属病院, 講師 (70467992)
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| Project Period (FY) |
2016-04-01 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | GM1ガングリオシドーシス / 遺伝・先天異常学 |
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| Outline of Final Research Achievements |
GM1 gangliosidosis is a type of lysosomal storage disease, which is caused by lack of lysosomal β-galactosidase activity, leading to progressive neurodegeneration due to massive accumulation of GM1 ganglioside in the brain. Here, we generated the GM1 gangliosidosis-derived iPSCs to elucidate the pathological mechanisms of neural dysfunction under the disease and to find new drug candidates. Neurons from the patients-derived iPSCs exhibited the GM1 ganglioside accumulation and impaired pre-synaptic function. High throughput drug screening system using the patient-derived neural cells found two compounds as novel drug candidates. These could significantly reduce GM1 ganglioside accumulation in vitro and in vivo, and restored the presynaptic dysfunction in the patient-derived neurons. Our findings demonstrated the potential value of the patients-derived iPSC lines for the cellular model of GM1 gangliosidosis and that two compounds are the potential candidates as drugs in the future.
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Report
(3 results)
Research Products
(7 results)
