Integration of Systems Biology and Pharmacoepidemiology for Drug Repurposing Research: Lessons From the Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) Study

Background: The Drug Repurposing for Effective Alzheimer’s Medicines (DREAM) study is a multidisciplinary collaborative study aimed at identifying drug repurposing candidates for Alzheimer’s disease and related dementia (ADRD). DREAM integrates hypothesis generation based on metabolomics and transcriptomics studies and subsequent hypothesis refinement based on rigorous pharmacoepidemiologic analyses.

Objectives: To describe key considerations for the design of rigorous multidisciplinary drug repurposing investigations and to summarize major contributions of the DREAM study for ADRD drug discovery. Researchers interested in use of large-scale real-world data for drug repurposing research will benefit from this session.

Description: Drug discovery for disease-modifying therapies for ADRD based on the traditional paradigm of experimental animal models has been disappointing. Members of the panel, who are key contributors to the DREAM study, will describe their novel alternative approach to drug discovery in ADRD. Specifically, the following topics will be covered: 1) considerations related to hypothesis generation based on identifying existing treatments that target genetic or environmental regulators of early molecular determinants of ADRD pathology for therapeutic repurposing (Dr. Thambisetty, 25 minutes), 2) key study design challenges in evaluating ADRD as the outcome observational studies using routinely collected healthcare data (Dr. Gerhard, 15 minutes), 3) results from the hypothesis refinement activities in DREAM using real-world data focusing on two contrasting case-examples: phosphodiesterase-5 inhibitors and hydroxychloroquine (Dr. Desai, 25 mins), 4) reflections on the importance of clinical input for designing drug repurposing studies and future directions (Dr. Segal, 10 minutes). The symposium will conclude with a session dedicated to address questions and comments from the attendees to facilitate discussion of all pertinent issues (15 mins).