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Drug repositioning and repurposing for Alzheimer disease

Ballard C, Aarsland D, Cummings J, O'Brien J, Mills R, Molinuevo JL, Fladby T, Williams G, Doherty P, Corbett A, Sultana J.

Abstract

Drug repositioning and repurposing can enhance traditional drug development efforts and could accelerate the identification of new treatments for individuals with Alzheimer disease (AD) dementia and mild cognitive impairment. Transcriptional profiling offers a new and highly efficient approach to the identification of novel candidates for repositioning and repurposing. In the future, novel AD transcriptional signatures from cells isolated at early stages of disease, or from human neurons or microglia that carry mutations that increase the risk of AD, might be used as probes to identify additional candidate drugs. Phase II trials assessing repurposed agents must consider the best target population for a specific candidate therapy as well as the mechanism of action of the treatment. In this Review, we highlight promising compounds to prioritize for clinical trials in individuals with AD, and discuss the value of Delphi consensus methodology and evidence-based reviews to inform this prioritization process. We also describe emerging work, focusing on the potential value of transcript signatures as a cost-effective approach to the identification of novel candidates for repositioning.

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Referencia

Ballard C, Aarsland D, Cummings J, O'Brien J, Mills R, Molinuevo JL, Fladby T, Williams G, Doherty P, Corbett A, Sultana J. Drug repositioning and repurposing for Alzheimer disease. Nat Rev Neurol. 2020 Sep 16.