Drug Repurposing

Drug repurposing (also known as drug repositioning ) is the process of re-examining a known drug for use in a different disease. Several FDA-approved drugs and abandoned compounds in the biotech and pharma portfolios have antibiotic activity and have already been tested in humans, with detailed information available on their clinical pharmacology, ideal formulation and dosing, or potential toxicities. Drug repurposing is fruitful because common molecular pathways contribute to different diseases.

What's Once was Old is New Again

Drug repurposing has an advantage over traditional de novo antibiotic discovery approaches in that it can significantly reduce the cost and development time of the new drug, a critical consideration to keep pace with the rapid evolution of new drug-resistant pathogens. As many compounds have demonstrated safety in humans, repurposing might negate the need for phase I clinical trials. Advances in genomics and bioinformatics facilitate antibiotic drug repurposing, via in silico structure or mechanism-based assays that work with virtual drug databases.

REPURPOSED DRUG BLOCKS ZIKA VIRUS

For All Practical (Re)purposes ...

CHARM Investigators have identified surprising activities of drug used in different fields of medicine for treating antibiotic-resistant pathogens. A cholesterol lowering drug candidate blocked the antioxidant pigment of MRSA, resensitizing it to killing by the oxidative burst of host phagocytic cells. Commonly prescribed statins, antiplatelet drugs and the breast cancer agent tamoxifen boosted neutrophil extracellular traps and helped clear resistant infections in mouse models. Nutritional compounds such as vitamin B3, or drugs used in traditional Chinese or Indian medicine such as anacardic acid from cashew nuts or clove bud oil interfered with bacterial virulence mechanisms or boosted immunity to help clear infection.

Challenges and Opportunities

Opportunities for drug repurposing are not limited to direct killing of the target microbe, but might involve sensitizing the pathogen to host immune defenses, boosting leukocyte antimicrobial activities, or increasing host cell resilience against the toxic effects of infection. CHARM Investigators are using sophisticated technologies including high-throughput cell-based phenotypic screens, induced pluripotent stem (iPS) cells, and human organoids to model the host-pathogen interface in a comprehensive manner to uncover useful but as yet unrecognized activities of existing drugs.

As Good as Gold for Parasites

CHARM investigators conducted a high-throughput screen for inhibitors for the protozoan parasite pathogen Entamoeba histolytica, and identified potent activity of the FDA-approved gold-containing arthritis drug auranofin. Subsequent studies showed activity against MRSA, giardia, lymphatic filariasis and onchocerciasis (river blindness). UC San Diego translational efforts have advanced through Phase 1 clinical trials to support repurposing auranofin as a broad-spectrum antiparasitic.

Read the original paper in Nature Medicine

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