A Logical Network-based Drug-screening Platform for Alzheimer's Disease Representing Pathological Features of Human Brain Organoids

Overview

Journal Nat Commun

Specialty Biology

Date 2021 Jan 13

PMID 33436582

Citations 78

Authors

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

Inhee Mook-Jung

Affiliations

Soon will be listed here.

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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