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

Cheng Y, Zamrini E, Ahmed A, Wu WC, Shao Y, Zeng-Treitler Q. Medication-Wide Association Study Plus (MWAS+): A Proof of Concept Study on Drug Repurposing. Medical sciences (Basel, Switzerland). 2022 Aug 31; 10(3).

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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.

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