title: Progress and challenges in the discovery of macrofilaricidal drugs.
abstract: Control of human filarial infections currently depends on chemotherapeutic strategies predominantly directed at microfilariae. Doxycycline therapy in an extended daily dose regimen sterilizes and kills adult stages, but the utility of this drug for routine field use remains an issue of concern. No macrofilaricidal drugs with efficacy after one or two doses are available for use, delaying the achievement of the elimination or eradication of onchocerciasis and lymphatic filariasis. Moxidectin, a macrocyclic lactone, is currently in clinical trials for onchocerciasis. A few other drugs that have already been approved for use in veterinary practice or in human medicine for other indications are available for investigation. Early drug discovery pipelines are poorly populated and the process of macrofilaricide discovery and development remains highly challenging. In particular, the lack of convenient, validated animal models in an antifilarial drug discovery pathway is an unresolved issue.
authors.affiliation: Institute of Parasitology, McGill University, 21111 Lakeshore Road, Ste-Anne-de-Bellevue QC, H9X 3V9, Canada. timothy.g.geary@mcgill.ca
authors.forename: Timothy G
authors.initials: TG
authors.lastname: Geary
authors.forename: Charles D
authors.initials: CD
authors.lastname: Mackenzie
mesh_terms: D000818:Animals; D002009:Brugia / Q000187:drug effects; D004318:Doxycycline / Q000627:therapeutic use; D055808:Drug Discovery; D004605:Elephantiasis, Filarial / Q000188:drug therapy* / Q000469:parasitology; D005369:Filaricides / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D007783:Lactones / Q000627:therapeutic use; D047028:Macrocyclic Compounds / Q000627:therapeutic use; D018942:Macrolides / Q000627:therapeutic use; D008842:Microfilariae / Q000187:drug effects*; D009854:Onchocerca / Q000187:drug effects; D009855:Onchocerciasis / Q000188:drug therapy* / Q000469:parasitology; D014958:Wuchereria bancrofti / Q000187:drug effects
chemical_list: D005369:Filaricides; D007783:Lactones; D047028:Macrocyclic Compounds; D018942:Macrolides; D004318:Doxycycline; C027837:moxidectin