| Project/Area Number |
18K07058
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 49030:Experimental pathology-related
|
|---|
| Research Institution | National Cardiovascular Center Research Institute |
|---|
Principal Investigator |
Yamamoto Yumi 国立研究開発法人国立循環器病研究センター, 研究所, 非常勤研究員 (10614927)
|
|---|
| Project Period (FY) |
2018-04-01 – 2021-03-31
|
| Project Status |
Completed (Fiscal Year 2020)
|
| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
|
|---|
| Keywords | 血管性認知症 / CADASIL / 血管平滑筋細胞 / Notch3 / 遺伝性脳小血管病 / 壁細胞 / 脳小血管病 / NOTCH3 / 脳梗塞 |
|---|
| Outline of Final Research Achievements |
The purpose of this study was to develop a novel treatment for the hereditary cerebral small vessel disease, CADASIL, using patient-derived induced pluripotent stem cells (iPSCs). We successfully established in vitro model of CADASIL which can recapitulate disease-specific features such as deposition of granular osmiophilic materials and abnormal actin cytoskeleton. The analysis of iPSC-derived mural cells, we identified PDGFRbeta as a possible target for a treatment of CADASIL. Indeed, PDGFRbeta inhibition improved differentiation defect of oligodendrocyte precursor cell in CADASIL.
|
| Academic Significance and Societal Importance of the Research Achievements |
申請者らのグループは、世界に先駆けてCADASIL患者由来のiPS細胞を用いた２つのin vitroの実験系で実際の病態を再現することに成功した 。さらに、申請者がCADASILの病態発生機序として着目している過剰PDGFRβシグナルによるOPCの分化障害は、近年注目されているOPCと白質障害の関係性を明らかにするうえでも有用であると考えられる。本研究により、治療薬候補が２つ見いだされており、さらなる研究による治療法の開発に期待がもてる。
|
