Medication-Wide Association Study Plus (MWAS+): A Proof of Concept Study on Drug Repurposing.
Med Sci (Basel)
; 10(3)2022 08 31.
Article
in En
| MEDLINE
| ID: mdl-36135833
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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Hydroxymethylglutaryl-CoA Reductase Inhibitors
/
Alzheimer Disease
Type of study:
Clinical_trials
/
Observational_studies
/
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Med Sci (Basel)
Year:
2022
Document type:
Article
Affiliation country: