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Title: iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease
Authors: Kondo, Takayuki
Imamura, Keiko
Funayama, Misato
Tsukita, Kayoko
Miyake, Michiyo
Ohta, Akira
Woltjen, Knut  kyouindb  KAKEN_id  orcid (unconfirmed)
Nakagawa, Masato  kyouindb  KAKEN_id  orcid (unconfirmed)
Asada, Takashi
Arai, Tetsuaki
Kawakatsu, Shinobu
Izumi, Yuishin
Kaji, Ryuji
Iwata, Nobuhisa
Inoue, Haruhisa  kyouindb  KAKEN_id  orcid (unconfirmed)
Author's alias: 近藤, 孝之
今村, 恵子
舟山, 美里
月田, 香代子
三宅, 美智世
井上, 治久
Issue Date: 21-Nov-2017
Publisher: Elsevier BV
Journal title: Cell Reports
Volume: 21
Issue: 8
Start page: 2304
End page: 2312
Abstract: In the process of drug development, in vitro studies do not always adequately predict human-specific drug responsiveness in clinical trials. Here, we applied the advantage of human iPSC-derived neurons, which offer human-specific drug responsiveness, to screen and evaluate therapeutic candidates for Alzheimer’s disease (AD). Using AD patient neurons with nearly 100% purity from iPSCs, we established a robust and reproducible assay for amyloid β peptide (Aβ), a pathogenic molecule in AD, and screened a pharmaceutical compound library. We acquired 27 Aβ-lowering screen hits, prioritized hits by chemical structure-based clustering, and selected 6 leading compounds. Next, to maximize the anti-Aβ effect, we selected a synergistic combination of bromocriptine, cromolyn, and topiramate as an anti-Aβ cocktail. Finally, using neurons from familial and sporadic AD patients, we found that the cocktail showed a significant and potent anti-Aβ effect on patient cells. This human iPSC-based platform promises to be useful for AD drug development.
Description: アルツハイマー病病因物質を低減させる既存薬カクテルの同定 --患者由来iPS細胞を用いた化合物スクリーニングとin vitroトライアル--. 京都大学プレスリリース. 2017-11-28.
Rights: © 2017 The Author(s). This is an open access article under the CC BY-NC-ND license (
DOI(Published Version): 10.1016/j.celrep.2017.10.109
PubMed ID: 29166618
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