A logical network-based drug-screening platform for Alzheimer's disease representing pathological features of human brain organoids.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33436582.
- Also identified by DOI 10.1038/s41467-020-20440-5 and PMC identifier 7804132.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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.
Medical subject headings
- Alzheimer Disease
- Brain
- Drug Evaluation, Preclinical
- Gene Regulatory Networks
- Organoids