Pathophysiology and drug development using iPS technology specific to mitochondrial mutation-related deafness

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K18294
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Juntendo University
• Principal Investigator: Arai Shinpei 順天堂大学, 医学部, 非常勤助手 (70836220)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: ミトコンドリア遺伝子 / 遺伝性難聴 / 疾患特異的iPS細胞

Outline of Final Research Achievements

The mitochondrial gene 1555A>G mutation has been identified as the cause of hereditary hearing loss that shows susceptibility to aminoglycosides. However, the pathology and effective drug treatment have not yet been discovered. Since induced pluripotent stem cells (iPS cells) can differentiate into various cells, it has become possible to analyze the phenotype of hearing loss by inducing differentiation of iPS cells into inner ear cells, which are the target of hearing loss. By applying a method for inducing differentiation of iPS cells into the inner ear that the applicant's research group developed independently (patent pending/Fukunaga, Stem Cell Reports, 2017), we established disease model cells derived from iPS cells from patients with the mitochondrial gene 1555A>G mutation, and have clarified the mechanism of susceptibility to aminoglycoside antibiotics and developed a new drug treatment.

Free Research Field

耳鼻咽喉科学

Academic Significance and Societal Importance of the Research Achievements

本研究はミトコンドリア遺伝子155A>G変異による遺伝性難聴の分子病態・機序を解明する突破口を切り開き、根本的治療の現実化に正面から取り組むもので、画期的な技術を駆使している。これらの画期的な企画はこれまで全く創造されていない極めて独創性の高い研究である。この技術が臨床に適用されると、聴覚医学に新しい局面を迎えることができる。難聴に悩み、苦しむ数百万人の患者への大きな福音となり、国民生活の質的向上をもたらす極めて有意義な研究である。