Sabahat Iqbal, Cristina Bonet Olivares, Laura Rizzo, Thomas D. Parker, CS Wong, Benjamin R. Underwood, James Carpenter, Ross Dunne, Vanessa Raymont, Alastair Reith, Catherine J. Mummery, Eric Karran, Fiona Ducotterd, Gordon Wilcock, Jeffrey L. Cummings, John T. O'Brien, Leah Mursaleen, L Schneider, Rik Vandenberghe, Malcolm Macleod, Zunera Khan, Paresh Malhotra, Suzanne Reeves
INTRODUCTION: There is an urgent need to identify effective, safe, and affordable treatments for Alzheimer's disease (AD). Funded by the UK National Institute for Health and Care Research (NIHR), we developed a systematic drug prioritization pipeline to identify repurposed drug candidates for inclusion in a planned platform trial for clinical AD. METHODS: The wider AD community was invited to propose compounds using a standardized proposal template. Fourteen proposals were presented to an international expert panel, who independently ranked compounds based on biological plausibility, preclinical efficacy, safety, and trial feasibility. Extended drug summaries were compiled for shortlisted compounds, supported by ReLiSyR, a machine learning-supported systematic review tool. RESULTS: Following review in a second panel meeting, independent re-ranking identified the following compounds: atomoxetine (1st), metformin (2nd), isosorbide mononitrate and levetiracetam (joint 3rd). DISCUSSION: This robust drug prioritization pipeline will speed the identification and progression of promising candidates for therapeutic evaluation.