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Medication-Wide Association Study Plus (MWAS+): A Proof of Concept Study on Drug Repurposing

Authors :
Yan Cheng
Edward Zamrini
Ali Ahmed
Wen-Chih Wu
Yijun Shao
Qing Zeng-Treitler
Source :
Medical Sciences, Vol 10, Iss 3, p 48 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

The high cost and time for developing a new drug or repositioning a partially-developed drug has fueled interest in “repurposing” drugs. Drug repurposing is particularly of interest for Alzheimer’s disease (AD) or AD-related dementias (ADRD) because there are no unrestricted disease-modifying treatments for ADRD. We have designed and pilot tested a 3-Step Medication-Wide Association Study Plus (MWAS+) approach to rigorously accelerate the identification of drugs with a high potential to be repurposed for delaying and preventing AD/ADRD: Step 1 is a hypothesis-free exploration; Step 2 is mechanistic filtering; And Step 3 is hypothesis testing using observational data and prospective cohort design. Our results demonstrated the feasibility of the MWAS+ approach. The Step 1 analysis identified potential candidate drugs including atorvastatin and GLP1. The literature search in Step 2 found evidence supporting the mechanistic plausibility of the statin-ADRD association. Finally, Step 3 confirmed our hypothesis that statin may lower the risk of incident ADRD, which was statistically significant using a target trial design that emulated randomized controlled trials.

Details

Language :
English
ISSN :
20763271
Volume :
10
Issue :
3
Database :
Directory of Open Access Journals
Journal :
Medical Sciences
Publication Type :
Academic Journal
Accession number :
edsdoj.8bd60a0cac304ab4a4b117ae536ccd71
Document Type :
article
Full Text :
https://doi.org/10.3390/medsci10030048