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

Authors:
Open Access
Publisher website
Google Scholar
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.
Funding Information
  • National Institute on Aging (1RF1AG069121, 1R01AG073474)
  • Office of Research and Development (1RF1AG069121, 1R01AG073474)
  • Health Services Research and Development (1RF1AG069121, 1R01AG073474)
  • Washington DC VA Medical Center (1RF1AG069121, 1R01AG073474)

This publication has 23 references indexed in Scilit: