Development of effective evaluation method of bezafibrate for the fatty acid metabolism disorders using the iPS cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K21179
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics; Embryonic/Neonatal medicine
• Research Institution: Shimane University
• Principal Investigator: Yamada Kenji 島根大学, 学術研究院医学・看護学系, 助教 (70624930)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: 脂肪酸代謝異常症 / ベザフィブラート / 代謝性ミオパチー / in vitro probe assay / 脂肪酸代謝能 / VLCAD欠損症 / CPT2欠損症

Outline of Final Research Achievements

Although bezafibrate has been reported as a hopeful drug for fatty acid oxidation disorders (FAOD) in in vitro, a clinical trial showed no obvious efficacy. However, the clinical symptom was clearly improved in some patients. Therefore, I thought that its efficacy could not be completely denied, and the measurement of fatty acid oxidation capacity might be inappropriate.
In this study, I initially planned to develop and investigate a method for predicting the efficacy of bezafibrate using iPS cells. However, as a result, I found that modified conventional methods using fibroblasts derived from patients with FAOD, such as in vitro probe assay and fatty acid oxidation flux, can partially predict the efficacy of bezafibrate.

Free Research Field

先天代謝異常症

Academic Significance and Societal Importance of the Research Achievements

本研究結果はベザフィブラートの有効性を患者細胞を用いて予測するだけでなく、他の治療候補薬剤の有効性を検討することにも応用できる。本研究で発展させた脂肪酸代謝能の測定技術は一度に数～十数種類の薬剤を簡便に調べることが出来る。つまり、現時点ではベザフィブラートも含めて証明された治療薬のない脂肪酸代謝異常症への治療薬を探索する際に、患者由来の培養細胞を用いることで、安全に多数の薬剤を網羅的に検討できる。
さらに、脂肪酸代謝異常症だけでなく、ミトコンドリア病といった他の先天代謝異常症の治療薬の有効性を調べることにも応用できると思われる。