Mechanism of emphysema formation by controlling the Keap1-Nrf2 system and its application to COPD treatment strategies

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08660
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Osaka City University
• Principal Investigator: ASAI KAZUHISA 大阪市立大学, 大学院医学研究科, 准教授 (10382053)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: COPD / Nrf2 / タバコ / バルドキソロン

Outline of Final Research Achievements

Bardoxolone methyl is a drug that intervenes in the Keap1-Nrf2 system and has shown significant improvement and tolerability in GFR in a phase 2 clinical trial in patients with diabetic nephropathy. In this study, we planned to investigate the emphysema-suppressing effect and emphysema treatment-effect of Bardoxolone methyl in smoking-exposed COPD model mice. We confirmed the tolerability of Bardoxolone methyl. We found that there was no spontaneous improvement in emphysema and alveolar destruction until 4 weeks after the end of smoking exposure, and we formulated an experimental protocol suitable for evaluating the therapeutic effect on emphysema. The experiment was started, but the experiment was not completed due to the lockdown of the animal experiment facility due to the outbreak caused by COVID19.

Free Research Field

呼吸器内科

Academic Significance and Societal Importance of the Research Achievements

本研究では喫煙曝露COPDモデルマウスにおけるバルドキソロンメチルの気腫化抑制効果、治療効果検討を計画した。本研究では、喫煙曝露終了後4週間までは自発的な気腫化、肺胞破壊の改善を認めないことを見出して、喫煙曝露COPDモデルマウスにおける気腫化治療効果の評価に適する実験プロトコールを策定した。今後、バルドキソロンメチルや他の治療候補物質での気腫化治療効果の検討を進める。