Development of a novel drug repositioning method considering Alzheimer's disease subtypes
| Project/Area Number |
20K15778
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 43060:System genome science-related
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| Research Institution | The University of Tokyo (2022)
Osaka University (2020-2021) |
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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)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| 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)
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| 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 |
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| 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。
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| 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.
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| 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。
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Report
(4 results)
Research Products
(26 results)
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[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
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Journal Title
Computational and Structural Biotechnology Journal
Volume: 20
Pages: 5296-5308
DOI
Related Report
Peer Reviewed / Open Access
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[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.
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Journal Title
Alzheimer's Research & Therapy
Volume: 13, 92
Issue: 1
DOI
Related Report
Peer Reviewed / Open Access
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[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
Int'l Joint Research
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