iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

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

Public transportation and the disabled person

機能訓練事業として実施している「生活リハビリ教室」の教室生208名を対象に，公共交通機関を利用して外出するために障害になっている要因を明らかにする目的で，郵送法による自記式アンケート調査を行った。回答は125名（60.1％）からあった。外出経験がある者は67名（53.6％）で外出経験がない者が58名であった。外出時に付添いが必要と思っている者は，外出経験のない者に多かった。公共交通機関を利用しての外出を阻害している要因には，乗り物の昇降口に段差があることや早く発車して危険である，また周囲の人に介助を依頼しにくいことなどが挙げられている。身体機能障害者が外出できない理由は個人によって異なってはいるが，地域社会に身体機能障害者を受け入れる環境を整えていく必要がある。A survey was distributed by mail to disabled people who received functional training in 1997. Of 208 questionnaires sent, 125 (60.1%) were returned. Sixty-seven (53.6%) of the respondents had experience traveled outside. People who participate in functional trainning for disability hope to have an attendant to accompany them when traveling. One primary factor that hinders traveling outside and using public transportation is that they cannot ask for help because of shyness. Another factor is the construction of entrances (e.g.,bumps) for vehicles which cannot be traversed easily. Reasons differed among those who had traveled outside and those who had not. It is necessary to prepare an environment (e.g., public transportationto) for ease of use for disabled persons in regional communities

Views on Childcare Students connected from Childcare Traning : With a Focus on Childcare Environment to keep the Security of the Children

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Modeling Alexander disease with patient iPSCs reveals cellular and molecular pathology of astrocytes

Alexander disease is a fatal neurological illness characterized by white-matter degeneration and formation of Rosenthal fibers, which contain glial fibrillary acidic protein as astrocytic inclusion. Alexander disease is mainly caused by a gene mutation encoding glial fibrillary acidic protein, although the underlying pathomechanism remains unclear. We established induced pluripotent stem cells from Alexander disease patients, and differentiated induced pluripotent stem cells into astrocytes. Alexander disease patient astrocytes exhibited Rosenthal fiber-like structures, a key Alexander disease pathology, and increased inflammatory cytokine release compared to healthy control. These results suggested that Alexander disease astrocytes contribute to leukodystrophy and a variety of symptoms as an inflammatory source in the Alexander disease patient brain. Astrocytes, differentiated from induced pluripotent stem cells of Alexander disease, could be a cellular model for future translational medicine

iPSC-Based Compound Screening and In Vitro Trials Identify a Synergistic Anti-amyloid β Combination for Alzheimer’s Disease

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.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