Novel therapeutic strategies for amyotrophic lateral sclerosis using human deciduous dental pulp stem cells and their active ingredients
| Project/Area Number |
17K19666
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
General internal medicine and related fields
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| Research Institution | Gifu Pharmaceutical University |
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Principal Investigator |
Hozimi Isao 岐阜薬科大学, 薬学部, 教授 (20242430)
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| Co-Investigator(Kenkyū-buntansha) |
栗田 尚佳 岐阜薬科大学, 薬学部, 講師 (00746315)
柴田 敏之 岐阜大学, 大学院医学系研究科, 教授 (50226172)
山本 朗仁 徳島大学, 大学院医歯薬学研究部(歯学域), 教授 (50244083)
神志那 弘明 岐阜大学, 応用生物科学部, 准教授 (50506847)
位田 雅俊 岐阜薬科大学, 薬学部, 准教授 (70512424)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2019: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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| Keywords | 筋萎縮性側索硬化症 (ALS) / ヒト乳歯歯髄幹細胞培養上清 (SHED-CM) / Cu/Zn SOD (SOD1） / 凝集体 / iPS細胞 / 筋萎縮性側索硬化症（ALS) / 筋萎縮性側索硬化症 / ヒト乳歯歯髄幹細胞培養上清 / 内科 / 脳・神経 / 脳・神経疾患 |
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| Outline of Final Research Achievements |
Motor neurons derived from patients with familial ALS are prone to aggregate formation and cell death. As A2a cells,a mouse neuroblastoma cells, into which the mutant SOD1 gene was incorporated, have shown intracellular aggregates and insoluble abnormal proteins, an ALS model cell system has been established. Administration of human deciduous dental pulp stem cell culture supernatant (SHED-CM) was found to suppress the accumulation of insoluble abnormal protein.In addition, ethanol extract components of Brazilian green propolis, as well as its selective components of kaempferol and also α7nAChR, a nicotinic acid receptor, have revealed to activate autophagy and suppress cell death. We have prepared differentiation to motor neurons using iPS cells derived from a patient with SOD1 mutation, a patient with sporadic ALS, and a healthy control.
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| Academic Significance and Societal Importance of the Research Achievements |
筋萎縮性側索硬化症（ALS）はこれまで多くの研究がなされ、モデル細胞やモデル動物を使って多くの創薬が提言されてきたが、ヒトにおいて臨床上満足のいく有効な薬剤は見出されていない。ヒトiPS細胞を使った研究は新たな創薬への道を切り開いている。ALSの病態は複数の要因が多面的に作用しており、単一薬剤での十分な有効性は得がたい。SHED-CMは多くの有効成分を含み、自然が作りだした複合剤で、神経難病への活用に期待が大きい。SHED-CMの有効性についてN2a細胞モデル系を使って証明し、作用機序、有効成分について検索した。ALS患者由来のiPS細胞についても準備し、創薬スクリーニング系を立ち上げた。
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Report
(4 results)
Research Products
(15 results)
