A logical network-based drug-screening platform for Alzheimer’s disease representing pathological features of human brain organoids

Jong-Chan Park, So-Yeong Jang, Dongjoon Lee, Jeongha Lee, Uiryong Kang, Hongjun Chang, Haeng Jun Kim, Sun-Ho Han, Jinsoo Seo, Murim Choi, Dong Young Lee, Min Soo Byun, Dahyun Yi, Kwang-Hyun Cho () and Inhee Mook-Jung ()
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Jong-Chan Park: College of Medicine, Seoul National University
So-Yeong Jang: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Dongjoon Lee: College of Medicine, Seoul National University
Jeongha Lee: College of Medicine, Seoul National University
Uiryong Kang: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Hongjun Chang: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Haeng Jun Kim: College of Medicine, Seoul National University
Sun-Ho Han: College of Medicine, Seoul National University
Jinsoo Seo: Department of Brain and Cognitive Science, Daegu Gyeongbuk Institute of Sciences and Technology (DGIST)
Murim Choi: College of Medicine, Seoul National University
Dong Young Lee: Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University
Min Soo Byun: Department of Neuropsychiatry, Seoul National University Bundang Hospital
Dahyun Yi: Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University
Kwang-Hyun Cho: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST)
Inhee Mook-Jung: College of Medicine, Seoul National University

Nature Communications, 2021, vol. 12, issue 1, 1-13

Abstract: Abstract 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.

Date: 2021
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DOI: 10.1038/s41467-020-20440-5

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