Drug development for mitochondrial disease based on sulfur metabolism

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K19521
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 52:General internal medicine and related fields
• Research Institution: Tohoku University (2019); Kumamoto University (2018)
• Principal Investigator: Wei Fanyan 東北大学, 加齢医学研究所, 教授 (90555773)
• Project Period (FY): 2018-06-29 – 2020-03-31
• Keywords: ミトコンドリア / ミトコンドリア病 / tRNA / 硫黄修飾

Outline of Final Research Achievements

Mitochondrial disease is a devastating genetic disease, which is mainly caused by the pathogenic mutations in mitochondrial DNA. Currently, there is no effective treatment that can cure the disease. This study is aimed to develop a functional screening system that leads to the discovery of drug target for the treatment of mitochondrial disease. In this study, we utilized a genome-wide shRNA lentiviral system and screened over 3,000 mitochondria-related genes in cell lines carrying pathogenic mitochondria DNA. We discovered a specific shRNA, which targets a gene involved in sulfur metabolism, was capable to upregulate mitochondrial reactive sulfur species as well as respiratory activity, thereby leading to an efficient energy metabolism. These results thus lay the foundation for novel and innovative drug development in near future.

Free Research Field

生理学

Academic Significance and Societal Importance of the Research Achievements

本研究から、硫黄代謝に関わる遺伝子がミトコンドリア病創薬において有力な標的であることが示唆された。今後は同遺伝子の抑制が個体においてもミトコンドリア機能改善効果を有するかを検証するとともに、同遺伝子産物に対する低分子阻害剤の開発を進める予定である。これらの研究開発により、ミトコンドリア機能を根底から改善しうる薬剤の創出が可能となり、指定難病であるミトコンドリア病に新たな希望をもたらすことができる。