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Initiate research programs for translational bioinformatics and network pharmacology to support rational drug repositioning and combination therapy from discovery through clinical development.
2022 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.B Achieved Initiate research programs for translational bioinformatics and network pharmacology... DN 2012 AD Summit: 4A, 4B, 4C, and 4D News: Precision medicine data dive shows water pill may be viable to test as Alzheimer’s treatment Highlight: Study of green tea and other molecules uncovers new therapeutic strategy for Alzheimer’s Highlight: Hydroxychloroquine lowers dementia risk in humans, improves molecular signs of Alzheimer’s in mouse and cell models 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 Repositioning 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 Select projects funded in FY21 Effects of cannabis on age-related cognitive decline and Alzheimers disease pathology Projects funded under PAR-20-156 Restoration of proteostasis to address co-occurring conditions in Down Syndrome Alzheimer's MultiOme Data Repurposing: Artificial Intelligence, Network Medicine, and Therapeutics Discovery 2016
Identification of at least 6 existing drugs suitable for repurposing and/or combination therapy for AD and ADRD prevention or treatment. The drugs selected for repurposing or combination therapy will be prioritized based on:
- evidence that they modulate disease relevant pathways/networks gained from computational and empirical approaches.
- preclinical proof-of-efficacy in a relevant model system.
- availability of biomarkers to monitor target engagement in humans.
- sufficient evidence of safety for the intended target population.
Summary of Key Accomplishments
Novel uses for existing and failed drugs can save time and cost in bringing new therapeutics to individuals. Investigators funded through NIA’s Drug Repurposing and Combination Therapy Development program, have identified over 20 FDA approved drugs with a potential to be repurposed in AD. An example is bumetanide, an FDA approved drug for the treatment of hypertension and edema; based on computational predictions that utilized publicly available genomic and EHR data and experimental work in animal models, this repurposing candidate has the potential to be effective in individuals with AD that carry the ApoE4 risk factor gene.
NIA’s Alzheimer’s Clinical Trials consortium and clinical trials funding initiatives provide a path for the most promising drug repurposing candidates to be evaluated in human trials for AD/ADRD treatment and prevention. NIA’s AD/ADRD clinical trials program has supported the testing of 10 repurposed drug candidates to date.
The key accomplishments summary is current as of March 2022.