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Two major human diseases caused by filariid nematodes are onchocerciasis, or river blindness, and lymphatic filariasis, which can lead to elephantiasis. The drugs ivermectin, diethylcarbamazine (DEC), and albendazole are used in control programs for these diseases, but are mainly effective against the microfilarial stage and have minimal or no effect on adult worms. Adult  Onchocerca volvulus  and  Brugia malayi  worms (macrofilariae) can live for up to 15 years, reproducing and allowing the infection to persist in a population. Therefore, to support control or elimination of these two diseases, effective macrofilaricidal drugs are necessary, in addition to current drugs. In an effort to identify macrofilaricidal drugs, we screened an FDA-approved library with adult worms of  Brugia  spp. and  Onchocerca ochengi , third-stage larvae (L3s) of  Onchocerca volvulus , and the microfilariae of both  O. ochengi  and  Loa loa . We found that auranofin, a gold-containing drug used for rheumatoid arthritis, was effective  in vitro  in killing both  Brugia  spp. and  O. ochengi  adult worms and in inhibiting the molting of L3s of  O. volvulus  with IC 50  values in the low micromolar to nanomolar range. Auranofin had an approximately 43-fold higher IC 50  against the microfilariae of  L. loa  compared with the IC 50  for adult female  O. ochengi , which may be beneficial if used in areas where  Onchocerca  and  Brugia  are co-endemic with  L. loa , to prevent severe adverse reactions to the drug-induced death of  L. loa  microfilariae. Further testing indicated that auranofin is also effective in reducing  Brugia  adult worm burden in infected gerbils and that auranofin may be targeting the thioredoxin reductase in this nematode.

Repurposing Auranofin as a Lead Candidate for Treatment of Lymphatic Filariasis and Onchocerciasis