What is it about?

Human diseases are complex biological phenomena resulting from perturbations of numerous signaling pathways. The complex nature of human diseases explains frequently observed marginal or transitory efficacy of mono-therapeutic interventions. For this reason, combination therapy is being increasingly evaluated as a biologically plausible strategy for reversing disease state. This paper describes how this strategy can be applied for fast and robust combinational drug repurposing for Alzheimer’s disease.

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Why is it important?

Genome-Wide Association Studies (GWAS) provide a prominent opportunity for disclosing human-specific signaling pathways that are enriched in disease-associated genes and include targets for approved drugs thereby allowing rational drug repurposing. We elaborated a universal computational platform that enables robust identification and therapeutic targeting of such signaling pathways. The experimental results of a proof-of-concept study applied to Alzheimer’s disease (AD) demonstrated feasibility and efficacy of the proposed approach for rapid development of synergistic drug combinations for common human diseases.

Perspectives

The idea that combining human genetics, network biology and drug repurposing should significantly speed up development of innovative combinational treatments has long been discussed. Our paper translates these theoretical considerations into practice. S. Nabirotchkine, co-founder of Pharnext company The proposed integrated approach supports the emerging trend to capitalize on a comprehensive and computerized knowledge of a disease derived from large-scale molecular data, to accelerate the identification of relevant therapeutic targets and the selection of drug candidates for clinical evaluation. Given the rapid emergence of approaches for systematic drug repurposing and combination, fast progress in this area will be assured by unbiased comparisons as well as integration of different methodological strategies. M. Guedj, Head of Biometrics, Data & Decision Sciences, Nanobiotix

Serguei Nabirotchkine
Pharnext

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This page is a summary of: Combinational Drug Repurposing from Genetic Networks Applied to Alzheimer’s Disease, Journal of Alzheimer s Disease, August 2022, IOS Press,
DOI: 10.3233/jad-220120.
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