Drug Repurposing: Multiscale models of disease

Expand existing and develop new systems biology and systems pharmacology research programs to build multiscale models of disease that will lead to the identification of networks/sub-networks as drug targets and readouts of therapeutic activity and advance the validation of existing and novel targets, rational drug repositioning and rational development of combination therapy.

2021 PAR-17-032: Translational Bioinformatics Approaches to Advance Drug Repositioning and Combination Therapy Development for Alzheimer’s Disease (R01) PAR-20-156: Translational Bioinformatics Approaches to Advance Drug Repositioning and Combination Therapy Development for Alzheimer’s Disease (R01 Clinical Trial Optional) PAR-25-374: Translational Bioinformatics and Experimental Approaches to Advance Drug Repositioning and Combination Therapy Development for Alzheimer’s Disease and Related Dementias (R01 Clinical Trial Not Allowed) 7.A Achieved Expand existing and develop new systems biology and systems pharmacology research programs... DN 2015 AD Summit: 1E, 2D, 2E, 2F, and 2G Workshop: Precision Medicine Approaches for Developing Combination Therapies for the Treatment and Prevention of Alzheimer's Disease (AD) and AD-Related Dementias Drug Repurposing and Combination Therapy Development Translational Bioinformatics Approaches to Advance Drug Repositioning and Combination Therapy Development for Alzheimer’s Disease Endophenotype Network-based Approaches to Prediction and Population-based Validation of in Silico Drug Repurposing for Alzheimer’s Disease Compound repositioning for Alzheimer’s Disease using knowledge graphs, insurance claims data, and gene expression complementarity Drug repurposing for Alzheimer's disease using structural systems pharmacology An Integrated Reverse Engineering Approach Toward Rapid drug Re positioning for Alzheimer's Disease Systematic Alzheimer's disease drug repositioning (SMART) based on bioinformatics-guided phenotype screening and image-omics ApoE Genotype-Directed Drug Repositioning and Combination Therapy for Alzheimer's Disease Harnessing Diverse BioInformatic Approaches to Repurpose Drugs for Alzheimers Disease NIA-AA Symposium: Enabling Precision Medicine for Alzheimer's Disease Through Open Science Select projects funded in FY21 Projects funded under PAR-20-156 Detecting synergistic effects of pharmacological and non-pharmacological interventions for AD/ADRD 2016

Launch at least 6 cross-disciplinary research programs that bring together experts in translational bioinformatics, computational biology, genetics, epidemiology, drug discovery and clinical research to develop a predictive model of the disease. Efforts should support:

• development of computational tools and infrastructure to allow basic and clinical researchers to query model in silico and validate it by using it for patient stratification, predictions of efficacy, on- and off-target adverse effects.
• identification of quantitative methods to access synergy between (1) multiple therapeutic agents and (2) pharmacologic/non-pharmacologic perturbations.
• development of phenotypic screens (in cell based and/or animal models) to advance rational drug repositioning and data-driven development of combination therapy based on the ability of individual or combinations of therapeutic agents to shift the network state away from disease.