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Drug target finding based on the analysis of real world data

Research Project

Project/Area Number 20H00491
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section一般
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionKyoto University

Principal Investigator

Kaneko Shuji  京都大学, 医学研究科, 研究員 (60177516)

Co-Investigator(Kenkyū-buntansha) 永安 一樹  京都大学, 薬学研究科, 助教 (00717902)
浅井 聰  日本大学, 医学部, 教授 (80231108)
浅岡 希美  京都大学, 医学研究科, 助教 (90826091)
Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2022: ¥14,170,000 (Direct Cost: ¥10,900,000、Indirect Cost: ¥3,270,000)
Fiscal Year 2021: ¥14,820,000 (Direct Cost: ¥11,400,000、Indirect Cost: ¥3,420,000)
Fiscal Year 2020: ¥16,120,000 (Direct Cost: ¥12,400,000、Indirect Cost: ¥3,720,000)
Keywordsリアルワールドデータ / レセプト / ビッグデータ / 電子カルテ / 薬理学 / 創薬 / 臨床検査値 / 臨床予測性 / 有害事象 / ドラッグリポジショニング / AI創薬
Outline of Research at the Start

本研究は、有害事象セルフレポート、レセプト記録、電子カルテの遡及的解析から特定の医薬品由来の有害事象を低減する併用薬を発見するドラッグリポジショニングを手がかりとして、有害事象の低減に関与する生体分子の同定を行い、類似症状を呈する自然発症疾患の新しい治療標的への応用を探る。すでに予備検討で有望な併用薬を見出している3テーマについて、データ解析による因果関係の検討、動物やヒト細胞を用いた実証実験、遺伝子発現解析やパスウェイ解析を行い、発症と薬物の作用メカニズムを明らかにする。本研究は実臨床記録の統計解析と薬理実証実験を組み合わせ、世界に類を見ない「臨床エビデンスに基づく創薬」を実現する。

Outline of Final Research Achievements

Using a method to discover drug combinations that reduce adverse events from clinical data analysis, we explored its application to new therapeutic targets for naturally occurring diseases that exhibit symptoms similar to those of adverse events. We targeted (1) dyslipidemia caused by olanzapine, (2) interstitial pneumonia caused by amiodarone, and (3) obsessive-compulsive disorder OCD caused by pramipexole. For (1), we discovered the usefulness of combined use of vitamin D and found skeletal muscle INSIG2 as a target. Regarding (2), we discovered that dabigatran has an anti-pulmonary fibrosis effect and found a therapeutic pathway mediated by the platelet-derived growth factor α receptor. Regarding (3), we discovered the usefulness of proton pump inhibitors and clarified the mechanism of suppressing OCD by lowering the pH within neurons of the lateral orbitofrontal cortex by inhibiting ATP4A.

Academic Significance and Societal Importance of the Research Achievements

本研究では国内外で公開されている大規模診療記録や有害事象に関連するビッグデータに着目し、統計学的手法を用いてそれらを解析・有効活用するとともに実証実験を行い、有害事象と類似した自然発症疾患の分子機序の解明や治療薬の開発を目指した。従来にはない研究戦略と実証的薬理学を組み合わせた計画が綿密に構築されており、有害事象を軽減する戦略や新規治療薬の創出に繋がると期待できる。また新しい創薬の方法論を創成できる可能性も高い。

Report

(5 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Annual Research Report
  • 2021 Annual Research Report
  • 2020 Comments on the Screening Results   Annual Research Report
  • Research Products

    (8 results)

All 2024 2023 2021 2020

All Journal Article (7 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 7 results,  Open Access: 7 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] A Novel Strategy for the Discovery of Drug Targets: Integrating Clinical Evidence with Molecular Studies2024

    • Author(s)
      Kaneko Shuji
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 47 Issue: 2 Pages: 345-349

    • DOI

      10.1248/bpb.b23-00831

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2024-02-01
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Amelioration of obsessive-compulsive disorder by intracellular acidification of cortical neurons with a proton pump inhibitor2024

    • Author(s)
      Hatakama Hikari、Asaoka Nozomi、Nagayasu Kazuki、Shirakawa Hisashi、Kaneko Shuji
    • Journal Title

      Translational Psychiatry

      Volume: 14 Issue: 1 Pages: 27-27

    • DOI

      10.1038/s41398-024-02731-3

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment2024

    • Author(s)
      Hideo Hagihara、Takao Keizo、他129名
    • Journal Title

      eLife

      Volume: 12 Pages: 89376-89376

    • DOI

      10.7554/elife.89376

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Vitamin D supplementation is effective for olanzapine-induced dyslipidemia2023

    • Author(s)
      Zhou Zijian、Nagashima Takuya、Toda Chihiro、Kobayashi Mone、Suzuki Takahide、Nagayasu Kazuki、Shirakawa Hisashi、Asai Satoshi、Kaneko Shuji
    • Journal Title

      Frontiers in Pharmacology

      Volume: 14 Pages: 1135516-1135516

    • DOI

      10.3389/fphar.2023.1135516

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Enhancement of adenosine A2A signaling improves dopamine D2 receptor antagonist-induced dyskinesia via β-arrestin signaling2023

    • Author(s)
      Nagaoka Koki、Asaoka Nozomi、Nagayasu Kazuki、Shirakawa Hisashi、Kaneko Shuji
    • Journal Title

      Frontiers in Neuroscience

      Volume: 16 Pages: 1082375-1082375

    • DOI

      10.3389/fnins.2022.1082375

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Drug Repurposing Prediction and Validation From Clinical Big Data for the Effective Treatment of Interstitial Lung Disease2021

    • Author(s)
      Siswanto Soni、Yamamoto Hiroki、Furuta Haruka、Kobayashi Mone、Nagashima Takuya、Kayanuma Gen、Nagayasu Kazuki、Imai Yumiko、Kaneko Shuji
    • Journal Title

      Frontiers in Pharmacology

      Volume: 12 Pages: 635293-635293

    • DOI

      10.3389/fphar.2021.635293

    • Related Report
      2021 Annual Research Report 2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Striatal TRPV1 activation by acetaminophen ameliorates dopamine D2 receptor antagonists-induced orofacial dyskinesia2021

    • Author(s)
      Nagaoka Koki、Nagashima Takuya、Asaoka Nozomi、Yamamoto Hiroki、Toda Chihiro、Kayanuma Gen、Siswanto Soni、Funahashi Yasuhiro、Kuroda Keisuke、Kaibuchi Kozo、Mori Yasuo、Nagayasu Kazuki、Shirakawa Hisashi、Kaneko Shuji
    • Journal Title

      JCI Insight

      Volume: in press Issue: 10 Pages: 1-16

    • DOI

      10.1172/jci.insight.145632

    • NAID

      120007038817

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Patent(Industrial Property Rights)] 遅発性ジスキネジアの治療又は予防用組成物、及び遅発性ジスキネジアを治療又は予防するための有効成分のスクリーニング方法2020

    • Inventor(s)
      金子周司他
    • Industrial Property Rights Holder
      金子周司他
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Acquisition Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas

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Published: 2020-04-28   Modified: 2025-01-30  

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