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
  • 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. [email protected].
  • 12. Department of Biochemistry and Biomedical Sciences, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. [email protected].
  • 13. Neuroscience Research Institute, Medical Research Center, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. [email protected].
  • 14. SNU Dementia Research Center, College of Medicine, Seoul National University, Seoul, 03080, Republic of Korea. [email protected].
PMID: 33436582 DOI: 10.1038/s41467-020-20440-5
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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