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2019 Fiscal Year Final Research Report

Elucidation of the pathological mechanism of KACh channelopathy and development of novel heart rate modulating drug

Research Project

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Project/Area Number 18K19547
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 53:Organ-based internal medicine and related fields
Research InstitutionOsaka University

Principal Investigator

Asano Yoshihiro  大阪大学, 医学系研究科, 講師 (60527670)

Project Period (FY) 2018-06-29 – 2020-03-31
Keywords希少難病 / 分子循環器学 / 徐脈性不整脈 / 洞不全症候群 / ゲノム解析 / 創薬開発
Outline of Final Research Achievements

We established KACh channelopathy, an inherited bradyarrhythmia consisting of sick sinus syndrome, atrioventricular block, and atrial fibrillation. Whole exome sequencing analysis was performed using a genomic cohort and pathogenic variants were identified among the genes associated with KACh channelopathy. We analysed the molecular mechanism of KACh channel-mediated regulation, assessed its function, and evaluated for drug efficacy by functional analysis and in vivo evaluation.

Free Research Field

循環器内科学

Academic Significance and Societal Importance of the Research Achievements

遺伝性徐脈性不整脈に対して安全かつ慢性期使用に耐え得る心拍増加薬はなく、侵襲を余儀なくされるペースメーカー等の対症治療に頼らざるを得ない。本研究において徐脈、房室ブロック、心房細動の原因となることを見出し、それらの原因となる遺伝要因を網羅的に探索しそれぞれの機能性変化を明確にすることで、新たな希少難病であるKAChチャネロパチーおよびその関連疾患の疾患概念の確立から臨床診断が可能となる。さらに疾患克服を目指すための治療標的探索を通じて、実臨床に還元できる治療法開発が可能となる。

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Published: 2021-02-19   Modified: 2023-01-30  

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