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  • Oxfendazole mediates macrofilaricidal efficacy against the filarial nematode Litomosoides sigmodontis in vivo and inhibits Onchocerca spec. motility in vitro.

Oxfendazole mediates macrofilaricidal efficacy against the filarial nematode Litomosoides sigmodontis in vivo and inhibits Onchocerca spec. motility in vitro.

PLoS neglected tropical diseases (2020-07-07)
Marc P Hübner, Coralie Martin, Sabine Specht, Marianne Koschel, Bettina Dubben, Stefan J Frohberger, Alexandra Ehrens, Martina Fendler, Dominique Struever, Edward Mitre, Nathaly Vallarino-Lhermitte, Suzanne Gokool, Sara Lustigman, Manfred Schneider, Simon Townson, Achim Hoerauf, Ivan Scandale
ABSTRACT

A major impediment to eliminate lymphatic filariasis and onchocerciasis is the lack of effective short-course macrofilaricidal drugs or regimens that are proven to be safe for both infections. In this study we tested oxfendazole, an anthelmintic shown to be well tolerated in phase 1 clinical trials. In vitro, oxfendazole exhibited modest to marginal motility inhibition of adult worms of Onchocerca gutturosa, pre-adult worms of Onchocerca volvulus and Onchocerca lienalis microfilariae. In vivo, five days of oral treatments provided sterile cure with up to 100% macrofilaricidal efficacy in the murine Litomosoides sigmodontis model of filariasis. In addition, 10 days of oral treatments with oxfendazole inhibited filarial embryogenesis in patent L. sigmodontis-infected jirds and subsequently led to a protracted but complete clearance of microfilaremia. The macrofilaricidal effect observed in vivo was selective, as treatment with oxfendazole of microfilariae-injected naïve mice was ineffective. Based on pharmacokinetic analysis, the driver of efficacy is the maintenance of a minimal efficacious concentration of approximately 100 ng/ml (based on subcutaneous treatment at 25 mg/kg in mice). From animal models, the human efficacious dose is predicted to range from 1.5 to 4.1 mg/kg. Such a dose has already been proven to be safe in phase 1 clinical trials. Oxfendazole therefore has potential to be efficacious for treatment of human filariasis without causing adverse reactions due to drug-induced microfilariae killing.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Lipid Mixture 1, Chemically Defined, liquid, sterile-filtered, BioReagent, suitable for cell culture
Corning® Transwell® polyester membrane cell culture inserts, 6.5 mm Transwell with 3.0 μm pore polyester membrane insert, TC-treated, sterile, 48/cs

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