2020 Fiscal Year Final Research Report

Challenge to development of new regenerative therapy targeting synapses between hair cells and auditory nerve fibers

Research Project

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Project/Area Number	17K19713
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Research Field	Surgery related to the biological and sensory functions and related fields
Research Institution	Yamagata University
Principal Investigator	Kakehata Seiji 山形大学, 医学部, 教授 (90261619)
Co-Investigator(Kenkyū-buntansha)	伊藤吏山形大学, 医学部, 准教授 (50344809) 杉山元康山形大学, 医学部, 医員 (60637255) 小泉優山形大学, 医学部, 非常勤講師 (80723585)
Project Period (FY)	2017-06-30 – 2021-03-31
Keywords	内耳 / 聴神経 / 有毛細胞 / シナプス / 再生 / 神経 / 再生医学 / ROCK阻害薬
Outline of Final Research Achievements	Inner ear regeneration is one of the unsolved themes in therapeutic research for hearing impairment. In this study, we challenged the development of a new therapeutic method targeting auditory nerve-inner hair cell synapses based on the new pathological concepts of primary neural degeneration and cochlear synaptopathy. Rho-associated coiled-coil containing protein kinase (ROCK) inhibitors has been reported to have neuroprotective and regenerative effects on synaptic pathways. Therefore, we analyzed the effect of ROCK inhibitions in a model of peripheral axonal damage in the spiral ganglion neurons induced by the glutamate agonists, N-methyl-D-aspartate (NMDA) and kainic acid in the explanted cochlea. This study suggested that ROCK inhibitors would be a potentially therapeutic candidate for the regeneration of peripheral axons and synaptic reformation in the cochlea.
Free Research Field	聴覚再生
Academic Significance and Societal Importance of the Research Achievements	聴覚障害に対する治療研究の中でも、内耳再生は極めて困難であると同時に、最も注目されているテーマの一つである。本研究ではprimary neural degenerationおよびcochlear synaptopathyという新しい病態概念に基づき、聴神経-有毛細胞間シナプスをターゲットした画期的な新規治療法の開発に挑戦した。本研究で用いたROCK阻害薬は、すでに臨床応用されている薬剤であり、臨床応用へのハードルも決して高くはないと考えられるため、これまで有効な治療法が存在しなった感音難聴に対する画期的な治療方法となることが期待される。