1. Academic Validation
  2. A logical network-based drug-screening platform for Alzheimer's disease representing pathological features of human brain organoids

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

  • Nat Commun. 2021 Jan 12;12(1):280. doi: 10.1038/s41467-020-20440-5.
Jong-Chan Park 1 2 3 4 So-Yeong Jang 5 Dongjoon Lee 1 3 Jeongha Lee 1 Uiryong Kang 5 Hongjun Chang 5 Haeng Jun Kim 1 3 Sun-Ho Han 1 2 3 Jinsoo Seo 6 Murim Choi 1 Dong Young Lee 7 8 9 Min Soo Byun 10 Dahyun Yi 7 Kwang-Hyun Cho 11 Inhee Mook-Jung 12 13 14
Affiliations

Affiliations

  • 1 Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
  • 2 Neuroscience Research Institute, Medical Research Center, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
  • 3 SNU Dementia Research Center, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea.
  • 4 Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, University College London, London, WC1N 3BG, United Kingdom.
  • 5 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea.
  • 6 Department of Brain and Cognitive Science, Daegu Gyeongbuk Institute of Sciences and Technology (DGIST), Daegu, 42988, Republic of Korea.
  • 7 Institute of Human Behavioral Medicine, Medical Research Center, Seoul National University, Seoul, 03080, Republic of Korea.
  • 8 Department of Psychiatry, College of medicine, Seoul National University, Seoul, 03080, Republic of Korea.
  • 9 Department of Neuropsychiatry, Seoul National University Hospital, Seoul, 03080, Republic of Korea.
  • 10 Department of Neuropsychiatry, Seoul National University Bundang Hospital, Seongnam, 13620, Republic of Korea.
  • 11 Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon, 34141, Republic of Korea. ckh@kaist.ac.kr.
  • 12 Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. inhee@snu.ac.kr.
  • 13 Neuroscience Research Institute, Medical Research Center, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. inhee@snu.ac.kr.
  • 14 SNU Dementia Research Center, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. inhee@snu.ac.kr.
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.

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