Filarial nematodes are human pathogens infecting around 157 million people throughout the tropics with over 1.5 billion people at risk of infection. Filariasis, accounts for some of the most debilitating global diseases that affect the ‘poorest of the poor’ resulting in a profound socio-economic impact on the most vulnerable in society. Mass Drug Administration (MDA) programmes, based on the generous donations of Mectizan® (Merk & Co. Inc), Albendazole (GSK) and diethycarbamazine (Eisai), are current strategies for filariasis control. The treatment is administered either singly or in combination and the drugs mainly target the microfilarial stage. Two major constraints of the programme are the absence of a drug with macrofilaricidal or permanent sterilizing activity; and concern over the potential development of drug resistance.
The anti-symbiotic treatment of filariasis programme aims to address the issues by developing treatments based on a novel approach: anti-symbiotic targeting of Wolbachia - a mutualistic bacterial endosymbiont of the worm, essential for worm development, fertility and survival. From field studies, a 6 week course of doxycycline has shown a persistent block in embryogenesis and macrofilaricidal activity. The programme combines novel drug discovery processes utilizing the latest technologies provided by post-genomic and computational bioinformatics and High Throughput Screening (HTS) technologies with more traditional screening systems established for the evaluation of macrofilaricidal drugs. In parallel, current regimes with antibiotics with proven efficiency will be refined to establish an optimal treatment which can be integrated into existing MDA programmes.
The outputs from A∙WOL I will progress through two paths. The first path will take the outputs from our focused and diversity library screening to deliver a novel pre-clinical candidate and a chemically distinct back-up within 36 months. The A∙WOL II Macrofilaricide Drug Discovery programme aims to progress the best outputs from the A∙WOL I screening campaigns through a rigorous lead optimization and candidate selection process.