Development of novel treatment of hereditary small vessel disease using iPSCs

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06983
• 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, 病院, 上級研究員 (10614927)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: CADASIL / small vessel disease / NOTCH3

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 treated CADASIL iPSC-derived Mural cells (MCs) and oligodendrocyte precursor cells (OPCs) with PDGFRbeta inhibitor and found that it can improve CADASIL phenotype to some extent. However, the inhibitor was not effective for the hypoxic stress response in CADASIL MCs, implying another signaling pathway involved in pathogenesis of CADASIL.

Free Research Field

Neurology

Academic Significance and Societal Importance of the Research Achievements

これまでに、CADASILの治療法として様々な薬剤が検討されてきたが、認知機能障害の原因
である脳卒中・白質障害を予防できる薬剤は依然として見つかっておらず、対症療法に終始してきた。本研究により、CADASIL治療薬の候補がいくつかみつかり、そのうちの１つについては、治験により一定の効果が認められることもわかった。これにより、難病の治療法開発に一歩近づいたといえる。