Construction of a new inner ear treatment strategy by orally administrable TrkB agonist

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K16895
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: The University of Tokyo
• Principal Investigator: Kinoshita Makoto 東京大学, 医学部附属病院, 登録診療員 (10755648)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 内耳障害 / 難聴 / めまい / BDNF / TrkB

Outline of Final Research Achievements

In this study, we examined the therapeutic effect of 7,8-Dihydroxyflavone (7,8-DHF), an orally available tropomyosin-receptor-kinase B (TrkB) agonist, on vestibular and cochlear injury animal models.
Oral administration of 7,8-DHF to gentamicin-induced vestibular disorder model animals showed preservation of ampullary nerves, increased spontaneous regeneration of vestibular hair cells, and synaptic remodeling between hair cells and ampullary nerves, and finally their vestibular function was improved.
On the other hand, in the noise-induced cochlear disorder model with oral administration of 7,8-DHF showed no significant ABR improvement effect and no histological protection or improvement effect on cochlear hair cells was obtained.

Free Research Field

神経耳科学

Academic Significance and Societal Importance of the Research Achievements

これまでの内耳障害治療は、不可逆的な聴覚・平衡障害をきたす恐れのある内耳局所の侵襲を伴う手法を余儀なくされ、臨床応用への高い障壁となっていた。
本研究では神経栄養因子BDNF類似のTrkB作動薬である7,8-DHFの経口投与により、薬剤性前庭障害が改善することを示した。本研究結果は新たな内耳障害の治療戦略として、7,8-DHFの経口投与が薬剤性や加齢性の平衡障害をはじめとする有毛細胞障害、求心性神経障害が病態の一つと考えられる全ての内耳障害の治療に結び付く可能性を示したという臨床応用的意義を持つ。