More than 2 billion people world-wide are estimated to be infected with parasitic nematodes, resulting in major economic and personal impacts from the years of life lost to poor health and premature mortality. The identification of drugs that can cheaply and effectively treat parasitic nematode infections is a critical global health need. However, the journey from initial drug development to approval for use in humans is long and costly, and screening directly on parasitic nematodes has intrinsic difficulties caused by the requirements for culturing and maintaining populations of parasites. It is likely that compounds that kill C. elegans will also kill parasitic nematodes, making C. elegans a cost-effective and rapid screening tool to identify new anthelmintics. To expedite the identification of drugs that can be rapidly translated into clinical use for parasite treatment, we are screening commercially available libraries of drugs approved for use in humans. These libraries represent drugs with known safety, bioavailability, and dosage information for use in humans that can be rapidly repurposed for treatment of parasitic nematode infections. Initial library screening has identified 92 compounds that kill C. elegans. These include known anthelmintics (Mebendazole, Pyrvinium pamoate, Tiabendazole, Niridazole, Levamisole, Pentamidine isethionate, Fenbendazole, Avermectin B1), as well as unexpected hits such as anti-Parkinsonian drugs. Numerous therapeutic groups are represented in the hits, including analgesics, antibacterial agents, antidepressants, antifungals, antihistamines, and antipsychotics. Continued testing will select for agents that are effective against multiple life stages (embryos, larval, dauer, and adult). Candidates will also be screened against databases of existing information to select agents with oral bioavailability, few side-effects in humans, and low cost for production. Compounds meeting these criteria will be given preference for follow-up testing. Our preliminary results indicate C. elegans may represent a powerful surrogate for large scale anti-nematode drug screening.

Affiliations:
- Geriatric Research Education and Clinical Center, VA Puget Sound Health Care System, Seattle, WA
- Department of Medicine, University of Washington, Seattle, WA