September 30, 2014
“Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis (Elephantiasis) and Onchocerciasis (River Blindness)”
Judy Sakanari, PhD
Center for Discovery and Innovation in Parasitic Diseases
Onchocerciasis or river blindness, and lymphatic filariasis, also known as elephantiasis, are two neglected tropical diseases that affect millions of people, primarily in developing countries. Currently, there are no drugs available that are effective against adult worms; existing drugs only kill the first-stage larvae (microfilariae). While these drugs can reduce transmission of infections in a population, the adult filarids (macrofilariae) can continue to produce microfilariae and perpetuate the cycle of infection.
To identify potential macrofilaricidal drugs, we developed a high throughput screen to test FDA-approved drugs on adult Brugia spp., which cause lymphatic filariasis and serve as a model for Onchocerca volvulus. From this screen we identified a drug called auranofin that kills these adult worms in vitro and in vivo. Auranofin is known to inhibit thioredoxin reductase, and subsequent testing of auranofin’s effects on Brugia’s thioredoxin reductase suggests that this may be the target in these filarid worms.
Dr. Judy Sakanari is a parasitologist at the Center for Discovery and Innovation in Parasitic Diseases at U.C. San Francisco. Her lab works on a number of parasitic diseases, and recently her team developed a low-cost, simple visual imaging system to assay an entire plate of worms based on phenotypic screening. The worm assay video imaging system, “The Worminator,” can be applied to the study of many macroparasites as well as other micro- and macroscopic organisms. She is currently collaborating with Dr. Bryan Bellaire, Veterinary Microbiology and Preventive Medicine at Iowa State University, on studies to formulate macrofilaricidal drugs.