Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
Neuroscience Research Institute, Medical Research Center, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
Nat Commun. 2021 Jan 12;12(1):280. doi: 10.1038/s41467-020-20440-5.
Developing effective drugs for Alzheimer's disease (AD), the most common cause of dementia, has been difficult because of complicated pathogenesis. Here, we report an efficient, network-based drug-screening platform developed by integrating mathematical modeling and the pathological features of AD with human iPSC-derived cerebral organoids (iCOs), including CRISPR-Cas9-edited isogenic lines. We use 1300 organoids from 11 participants to build a high-content screening (HCS) system and test blood-brain barrier-permeable FDA-approved drugs. Our study provides a strategy for precision medicine through the convergence of mathematical modeling and a miniature pathological brain model using iCOs.
开发治疗阿尔茨海默病（AD）的有效药物一直很困难，因为这种疾病的发病机制很复杂。AD 是痴呆症最常见的病因。在此，我们报告了一种高效的、基于网络的药物筛选平台，该平台是通过将 AD 的数学建模和病理特征与人类诱导多能干细胞衍生的脑类器官（iCOs），包括 CRISPR-Cas9 编辑的同基因系整合起来而开发的。我们使用 11 名参与者的 1300 个类器官来构建高内涵筛选（HCS）系统，并测试血脑屏障通透性的 FDA 批准药物。我们的研究通过将数学建模和使用 iCOs 的微型病理脑模型相结合，为精准医学提供了一种策略。
