A∙WOL Programme

Funded by the Bill & Melinda Gates Foundation, the aim of the A∙WOL programme is to develop new treatments against Wolbachia - a bacterial endosymbiont of filarial nematodes responsible for onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis). This will be achieved through the development of technologies and tools to identify and evaluate novel drugs and targets, and to develop and refine existing drugs and regimes.

                                                         Why?


Filarial nematodes are an important group of human pathogens infecting around 150 million people throughout the tropics with more than 1.5 billion 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. Control of filariasis currently relies on mass drug administration (MDA) programmes based on the generous drug donation programmes for Mectizan® (ivermectin - Merck and Co. Inc) and albendazole (GlaxoSmithKline). These drugs are administered either singly (ivermectin for onchocerciasis) or in combination (for lymphatic filariasis in Africa, or with diethylcarbamazine [DEC] for the rest of the world) by community-directed treatment. As these strategies principally target the microfilarial stage they need to be sustained for extended periods to cover the reproductive lifespan of the long-lived adult worms, with high population coverage to interrupt transmission. Programmes for onchocerciasis control, (APOC and OEPA) together with lymphatic filariasis (GPELF) have been established to promote and sustain the application of MDA to affected communities. Two of the major constraints of programme success are: (i) the absence of a drug with macrofilaricidal or permanent sterilizing activity and (ii) serious concern over the possibility of drug-resistance developing against the existing treatments.

 

The A∙WOL Consortium aims to address these issues by developing treatments based on a novel approach: anti-symbiotic targeting of Wolbachia - a mutualistic bacterial endosymbiont of filariae essential for worm development, fertility and survival and a component of inflammatory disease pathogenesis.

 

How?


The proposal combines novel drug discovery processes utilising the latest technologies provided by post-genomic and computational bioinformatics and HTS technologies with more traditional screening systems established for the evaluation of macrofilaricidal drugs. As with any drug discovery and development programme we recognise the inherent risks of a successful outcome dependent upon these approaches. Therefore, in parallel we propose to refine regimes of existing antibiotics with proven efficacy to establish an optimal treatment, which can integrate within existing frameworks for disease control.

The principal goal is the establishment of anti-symbiotic chemotherapy directed against Wolbachia compatible with control programmes for human filariasis. The expected health outcome would be an alternative treatment for human filariasis to ensure that the long-term goal of global elimination of this public health problem is achieved.

 

A secondary goal is the establishment of anti-symbiotic chemotherapy suitable for a more restricted use, planned for an interim phase in which there is yet no drug or drug combination available that is compatible with control programme usage.

 

These goals are aimed at addressing the priority strategies of the Bill & Melinda Gates Foundation’s Global Health programme for Onchocerciasis and Lymphatic Filariasis by “Improving treatment outcomes through research to develop a macrofilaricide drug that can eliminate the worm” and by “Eliminating transmission and/or disease by developing sustainable approaches for making better use of available drugs and drug combinations.”

 

                                                            A∙WOL Objectives


                 The project is divided into four objectives – click on an objective to learn more about our plans: