Advanced personalized medicine for therapeutic drug monitoring based on quantification of plasma exosomal miRNAs

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K19339
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 47:Pharmaceutical sciences and related fields
• Research Institution: Kyushu University
• Principal Investigator: Ieiri Ichiro 九州大学, 大学病院, 大学院担当教授 (60253473)
• Co-Investigator(Kenkyū-buntansha): 廣田 豪 九州大学, 大学病院, 副薬剤部長 (80423573) ; 田畑 香織 (佐々木香織) 九州大学, 薬学研究院, 助教 (90464388)
• Project Period (FY): 2021-07-09 – 2023-03-31
• Keywords: 薬物トランスポーター / exosome / miRNA

Outline of Final Research Achievements

In this study, we demonstrated that serum-derived exosomes regulate the expression of drug transporters that contribute to the distribution of drugs to the blood-brain barrier (BBB), and investigated the expression of miRNAs in exosomes derived from serum and BBB cells. Our results showed that the expression of multidrug resistance protein (MRP), a drug transporter known to be highly expressed in the BBB, was increased by the exposure of serum-derived exosomes. In addition, a miRNA array using exosomes detected miRNAs with more than a two-fold difference in expression between serum and BBB. miRNA binding prediction database (miRWalk, miRDB, TargetScan) analysis predicted that this miRNA bind to MRP mRNA.

Free Research Field

薬物動態学

Academic Significance and Societal Importance of the Research Achievements

薬物動態の個人差が大きい薬物については、治療薬物モニタリング (Therapeutic Drug Monitoring：TDM)が重要な役割を果たす。その一方で、薬物の標的臓器への分布は、血中濃度からは十分な予測が難しいのが現状である。本研究成果を基盤として、TDM残余検体を用いたexosome内miRNAの定量解析を進めることにより、従来の血中濃度測定に基づくTDMを更に発展させ、exosome内miRNAの解析によりBBBによる薬物トランスポーター機能を予測することで、薬物の脳移行を考慮した精度の高い個別化薬物治療の実現が期待できる。