Authors
K L Johnston1; L Ford1; J D Turner1; G Aljayyoussi1; W D Hong2; G L Nixon2; N G Berry2; P M O'Neill2; S A Ward1; M J Taylor1; 1 Liverpool School of Tropical Medicine; 2 University of Liverpool Discussion
Lymphatic filariasis and onchocerciasis are debilitating Neglected Tropical Diseases infecting approximately 150 million people. Current control programmes are hampered by the lack of a macrofilaricidal drug capable of safely killing the long-lived adult worms. Targeting Wolbachia, the essential bacterial symbionts of filariae, provides safe macrofilaricidal activity with superior outcomes compared to standard treatments. The broad-spectrum antibiotic doxycycline is macrofilaricidal, but requires a treatment regimen of at least four weeks duration. The Anti-Wolbachia (A∙WOL) drug discovery and development programme aims to deliver a new oral drug that delivers macrofilaricidal activity with ≤7 days treatment. The A∙WOL Consortium is currently engaged in: discovery of novel anti-Wolbachia compounds through High Throughput Screening of large diversity libraries; lead optimisation of lead series using iterative cycles of medicinal chemistry and biological testing; preclinical optimisation, using in vivo efficacy testing of regimens of anti-Wolbachia antibiotics and combinations and clinical trials. This approach has led thus far to the selection of three pre-clinical candidates: a new macrolide, TylaMac™, as well as two re-purposed registered drugs, high dose rifampicin and fusidic acid. Here we discuss the current A·WOL portfolio and their development towards clinical candidates. 
