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Development of a novel drug repositioning method considering Alzheimer's disease subtypes

Research Project

Project/Area Number 20K15778
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43060:System genome science-related
Research InstitutionThe University of Tokyo (2022)
Osaka University (2020-2021)

Principal Investigator

Kikuchi Masataka  東京大学, 大学院新領域創成科学研究科, 特任准教授 (90722538)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2022: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2021: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2020: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsアルツハイマー病 / ドラッグリポジショニング / サブタイプ / サブタイピング / 疾患サブタイプ
Outline of Research at the Start

現在アルツハイマー病 (AD:Alzheimer's Disease) の新薬開発は難航している。効率的な薬剤探索の手法の一つとして既存の薬剤から新たな薬効を見出し別の疾患へ応用するドラッグリポジショニング (DR:Drug Repositioning) が注目されている。遺伝子発現データを用いたDR手法が提案されてきたが、遺伝子発現データはしばしば再現性が低く、また遺伝子間の関係性も十分に考慮されていない。そこで本研究ではADオミックスデータによるメタアナリシス統計量とADに特化した生体分子ネットワークデータを駆使しADに特化した精度の高いDRを目指す。

Outline of Final Research Achievements

In this project, we performed a drug repositioning analysis using biomolecular network information. In our drug repositioning analysis, we were able to identify candidate genes that are plausible drug targets by considering the network information, and also identified existing drugs that target these genes. As Alzheimer's disease is a brain disease, there is the hurdle of drugs having to cross the brain-blood barrier. In the future, it is necessary to improve this method by taking into account the mechanism of action and molecular mechanism of drugs, and to experimentally verify the validity of the obtained drugs.

Academic Significance and Societal Importance of the Research Achievements

ADをはじめとする認知症の罹患者数は増加の一途を辿っており、その根本治療は多くの患者の悲願である。しかし、初めて症例が確認されてから120年経った今もなお、ADの根本治療薬開発は難航している。2023年1月に新薬が米国食品医薬品局に承認されたが、一定の有害事象も報告されているため多角的な創薬戦略が必要である。本研究手法を改良していくことで新たな薬剤探索が可能になると考えられる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (26 results)

All 2023 2022 2021 2020

All Journal Article (15 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 15 results,  Open Access: 14 results) Presentation (11 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] The clinical application of optimized AT(N) classification in Alzheimer’s clinical syndrome (ACS) and non-ACS conditions2023

    • Author(s)
      Kasuga Kensaku、Tsukie Tamao、Kikuchi Masataka、Tokutake Takayoshi、Washiyama Kazuo、Shimizu Soichiro、Yoshizawa Hiroshi、Kuroha Yasuko、Yajima Ryuji、Mori Hiroshi、Arakawa Yasuaki、Onda Kiyoshi、Miyashita Akinori、Onodera Osamu、Iwatsubo Takeshi、Ikeuchi Takeshi
    • Journal Title

      Neurobiology of Aging

      Volume: 127 Pages: 23-32

    • DOI

      10.1016/j.neurobiolaging.2023.03.007

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of mild cognitive impairment subtypes predicting conversion to Alzheimer’s disease using multimodal data2022

    • Author(s)
      Kikuchi M, Kobayashi K, Itoh S, Kasuga K, Miyashita A, Ikeuchi T, Yumoto E, Kosaka Y, Fushimi Y, Takeda T, Manabe S, Hattori S; Alzheimer's Disease Neuroimaging Initiative; Nakaya A, Kamijo K, Matsumura Y
    • Journal Title

      Computational and Structural Biotechnology Journal

      Volume: 20 Pages: 5296-5308

    • DOI

      10.1016/j.csbj.2022.08.007

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Construction of prediction models for growth traits of soybean cultivars based on phenotyping in diverse genotype and environment combinations2022

    • Author(s)
      Manggabarani Andi Madihah、Hashiguchi Takuyu、Hashiguchi Masatsugu、Hayashi Atsushi、Kikuchi Masataka、Mustamin Yusdar、Bamba Masaru、Kodama Kunihiro、Tanabata Takanari、Isobe Sachiko、Tanaka Hidenori、Akashi Ryo、Nakaya Akihiro、Sato Shusei
    • Journal Title

      DNA Research

      Volume: 29 Issue: 4

    • DOI

      10.1093/dnares/dsac024

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Different AT(N) profiles and clinical progression classified by two different N markers using total tau and neurofilament light chain in cerebrospinal fluid2022

    • Author(s)
      Kasuga Kensaku、Kikuchi Masataka、Tsukie Tamao、Suzuki Kazushi、Ihara Ryoko、Iwata Atsushi、Hara Norikazu、Miyashita Akinori、Kuwano Ryozo、Iwatsubo Takeshi、Ikeuchi Takeshi、collaboration author: Masaki Ikeda
    • Journal Title

      BMJ Neurology Open

      Volume: 4 Issue: 2 Pages: e000321-e000321

    • DOI

      10.1136/bmjno-2022-000321

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genetics of Alzheimer’s disease: an East Asian perspective2022

    • Author(s)
      Miyashita Akinori、Kikuchi Masataka、Hara Norikazu、Ikeuchi Takeshi
    • Journal Title

      Journal of Human Genetics

      Volume: 68 Issue: 3 Pages: 115-124

    • DOI

      10.1038/s10038-022-01050-z

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Retinoic Acid Deficiency Underlies the Etiology of Midfacial Defects2022

    • Author(s)
      Wu Y.、Kurosaka H.、Wang Q.、Inubushi T.、Nakatsugawa K.、Kikuchi M.、Ohara H.、Tsujimoto T.、Natsuyama S.、Shida Y.、Sandell L.L.、Trainor P.A.、Yamashiro T.
    • Journal Title

      Journal of Dental Research

      Volume: In press Issue: 6 Pages: 686-694

    • DOI

      10.1177/00220345211062049

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Upregulated expression of a subset of genes in APP;ob/ob mice: Evidence of an interaction between diabetes‐linked obesity and Alzheimer’s disease2021

    • Author(s)
      Shinohara Mitsuru、Kikuchi Masataka、Onishi‐Takeya Miyuki、Tashiro Yoshitaka、Suzuki Kaoru、Noda Yasuhiro、Takeda Shuko、Mukouzono Masahiro、Nagano Seiichi、Fukumori Akio、Morishita Ryuichi、Nakaya Akihiro、Sato Naoyuki
    • Journal Title

      FASEB BioAdvances

      Volume: - Issue: 5 Pages: 323-333

    • DOI

      10.1096/fba.2020-00151

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide copy number variation analysis of hepatitis B infection in a Japanese population2021

    • Author(s)
      Kikuchi M, Kobayashi K, Nishida N, Sawai H, Sugiyama M, Mizokami M, Tokunaga K, Nakaya A
    • Journal Title

      Human Genome Variation

      Volume: 8 Issue: 1 Pages: 22-22

    • DOI

      10.1038/s41439-021-00154-w

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Artificial intelligence-based computational framework for drug-target prioritization and inference of novel repositionable drugs for Alzheimer’s disease2021

    • Author(s)
      Tsuji, S., Hase, T., Yachie-Kinoshita, A., Nishino, T., Ghosh, S., Kikuchi, M., Shimokawa, K., Aburatani, H., Kitano, H. & Tanaka, H.
    • Journal Title

      Alzheimer's Research & Therapy

      Volume: 13, 92 Issue: 1

    • DOI

      10.1186/s13195-021-00826-3

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Synergistic role of retinoic acid signaling and Gata3 during primitive choanae formation2021

    • Author(s)
      Kurosaka Hiroshi、Mushiake Jin、Saha Mithun、Wu Yanran、Wang Qi、Kikuchi Masataka、Nakaya Akihiro、Yamamoto Sayuri、Inubushi Toshihiro、Koga Satoshi、Sandell Lisa L、Trainor Paul A、Yamashiro Takashi
    • Journal Title

      Human Molecular Genetics

      Volume: 30 Issue: 24 Pages: 2383-2392

    • DOI

      10.1093/hmg/ddab205

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Methylation Analysis in Monozygotic Twins With Treatment-Resistant Schizophrenia and Discordant Responses to Clozapine.2021

    • Author(s)
      Kikuchi M, Nakazawa T, Kinoshita M, Yamamori H, Yasuda Y, Fujimoto M, Hashimoto R, Numata S
    • Journal Title

      Frontiers in Psychiatry

      Volume: 12 Pages: 734606-734606

    • DOI

      10.3389/fpsyt.2021.734606

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] 1q21.1 distal copy number variants are associated with cerebral and cognitive alterations in humans2021

    • Author(s)
      Van der Meer D, Kikuchi M (70 in 143 authors), Boen R.
    • Journal Title

      Translational Psychiatry

      Volume: 11 Issue: 1 Pages: 182-182

    • DOI

      10.1038/s41398-021-01213-0

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Effects of copy number variations on brain structure and risk for psychiatric illness: Large‐scale studies from the ENIGMA working groups on CNVs2021

    • Author(s)
      Sonderby I, ... , for the ENIGMA-CNV Working Group (Kikuchi M (16 in 31 authors)) and ENIGMA 22q11.2 Deletion Syndrome Working Group.
    • Journal Title

      Human Brain Mapping

      Volume: NA Issue: 1 Pages: 300-328

    • DOI

      10.1002/hbm.25354

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Polygenic Architecture of Human Neuroanatomical Diversity2020

    • Author(s)
      Biton Anne, Kikuchi Masataka (13 of 25 authors), Toro Roberto
    • Journal Title

      Cerebral Cortex

      Volume: 30 Issue: 4 Pages: 2307-2320

    • DOI

      10.1093/cercor/bhz241

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Association of Copy Number Variation of the 15q11.2 BP1-BP2 Region With Cortical and Subcortical Morphology and Cognition2020

    • Author(s)
      Writing Committee for the ENIGMA-CNV Working Group、van der Meer Dennis、S?nderby Ida E.、Kaufmann Tobias、Walters G. Bragi、...、Fukunaga Masaki、....、Hashimoto Ryota、...、Dale Anders M.、Djurovic Srdjan、Agartz Ingrid、Westlye Lars T.、Stefansson Hreinn、Stefansson K、Thompson Paul M.、Andreassen Ole A.
    • Journal Title

      JAMA Psychiatry

      Volume: 77 Issue: 4 Pages: 420-420

    • DOI

      10.1001/jamapsychiatry.2019.3779

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] シングルセルオミックスデータを用いたアルツハイマー病の層別化解析2022

    • Author(s)
      菊地正隆
    • Organizer
      第 95 回日本生化学会大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Polygenic risk effect of Alzheimer’s disease in the Japanese population2022

    • Author(s)
      Masataka Kikuchi
    • Organizer
      4th Japan-UK Neuroscience Symposium 2022
    • Related Report
      2022 Annual Research Report
  • [Presentation] マルチモーダルデータとゲノミクスに基づいた認知症サブタイピング解析2022

    • Author(s)
      菊地正隆
    • Organizer
      第11回生命医薬情報学連合大会
    • Related Report
      2022 Annual Research Report
  • [Presentation] Identification of mild cognitive impairment subtypes predicting conversion to Alzheimer’s disease using a heterogeneous mixture learning2022

    • Author(s)
      菊地 正隆
    • Organizer
      International Symposium on Artificial Life and Robotics(AROB)
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 認知症ポリジェニック解析による病態の層別化2021

    • Author(s)
      菊地 正隆
    • Organizer
      第40回日本認知症学会 学術集会
    • Related Report
      2021 Research-status Report
  • [Presentation] AI技術を活用した認知症の発症リスク予測とその不均一性の理解2021

    • Author(s)
      菊地 正隆
    • Organizer
      第94回生化学会大会シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] 軽度認知障害のデータドリブンなサブタイピングおよびアルツハイマー病発症予測2020

    • Author(s)
      菊地 正隆、小林 香織、春日 健作、宮下 哲典、池内 健、湯本 英二、伏見 泰人、武田 理宏、真鍋 史朗、上條 憲一、松村 泰志
    • Organizer
      第39回日本認知症学会学術集会
    • Related Report
      2020 Research-status Report
  • [Presentation] An application of heterogeneous mixture learning for mild cognitive impairment subtyping2020

    • Author(s)
      Masataka Kikuchi, Kaori Kobayashi, Kensaku Kasuga, Akinori Miyashita, Takeshi Ikeuchi, Eiji Yumoto, Yasuto Fushimi, Toshihiro Takeda, Shirou Manabe, for the Alzheimer’s Disease Neuroimaging Initiative, Kenichi Kamijo, Yasushi Matsumura
    • Organizer
      11th Biennial Conference of the Asia-Pacific Association for Medical Informatics (APAMI 2020)
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] アルツハイマー病マルチオミックスデータを用いたシステム生物学的研究2020

    • Author(s)
      菊地 正隆
    • Organizer
      第93回日本生化学会大会
    • Related Report
      2020 Research-status Report
  • [Presentation] Polygenic analysis of Alzheimer’s disease in a Japanese population2020

    • Author(s)
      Masataka Kikuchi, Akinori Miyashita, Norikazu Hara, Daichi Shigemizu, Kouichi Ozaki, Shumpei Niida, Takechi Ikeuchi, Akihiro Nakaya
    • Organizer
      The Alzheimer's Association International Conference
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] 異種混合学習を用いたアルツハイマー病発症予測解析2020

    • Author(s)
      菊地 正隆,小林 香織,湯本 英二,伏見 泰人,武田 理宏, 真鍋 史朗,松村 泰志,上條 憲一,中谷 明弘
    • Organizer
      第24回日本医療情報学会春季学術大会
    • Related Report
      2020 Research-status Report

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Published: 2020-04-28   Modified: 2024-01-30  

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