Authors

S A Ward¹; P O'Neil²; J D Turner¹; M J Taylor¹;  ¹ Liverpool School of Tropical Medicine;  ² University of Liverpool

Discussion

Onchocerciasis and lymphatic filariasis (LF) are priority neglected tropical diseases targeted for elimination. In both cases the filarial parasites harbor a symbiotic endobacterium, Wolbachia. Targeting Wolbachia with an antibiotic such as doxycycline results in a macrofilaricidal effect. The A.WOL consortia was established to look for new anti-Wolbachia based treatments that could reduce treatment timeframes and that could be deployed in children and pregnant women. The consortia has screened over 1.8 million compounds for in vitro anti-wolbachia activity the hits of which have been progressed through standard pipelines to deliver the next generation of marofilaricide. The outputs of this endeavor include three new repurposing opportunities, two new drug candidates in formal development and dozens of novel lead series ready for development. The establishment of a validated translational path for macrofilaricides has highlighted the critical importance of PK/PD relationships, model selection and model to human bridging studies in de-risking the drug discovery process. These key determinants of success will be described with appropriate examples.