@article{oai:tsukuba.repo.nii.ac.jp:00044461, author = {Kondo, Takayuki and Imamura, Keiko and Funayama, Misato and Tsukita, Kayoko and Miyake, Michiyo and Ohta, Akira and Woltjen, Knut and Nakagawa, Masato and Asada, Takashi and Arai, Tetsuaki and Kawakatsu, Shinobu and Izumi, Yuishin and Kaji, Ryuji and Iwata, Nobuhisa and Inoue, Haruhisa}, issue = {8}, journal = {Cell Reports}, month = {Nov}, note = {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.}, pages = {2304--2312}, title = {iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease}, volume = {21}, year = {2017} }