The A·WOL Consortium are currently operating the following projects. If you are interested in collaborating with A·WOL, please contact us.
A·WOL II: Macrofilaricide Drug Discovery – The aim of this project is to progress the best outputs from the A∙WOL I screening campaigns through a rigorous lead optimization and candidate selection process in order to deliver novel pre-clinical candidates and a chemically distinct back-up. The pre-clinical candidates will have the potential for full development as a monotherapy in the first instance. A·WOL will undertake the optimization of lead series emerging from three independent hit finding campaigns. These programmes will be developed in competition with each other and against our Target Candidate Profile (TCP) that is aligned with established Target Product Profiles for a new anti-Wolbachia based macrofilaricide. To compliment these activities A·WOL will also undertake additional targeted screening activities with the specific aim of identifying hits with significant improvements in anti-Wolbachia activity and times to cure compared with the other leads in the portfolio. These would need to be seen as game-changing molecules in terms of anti-Wolbachia based macrofilaricide drug development.
A·WOL II: Macrofilaricide Drug Development – The project aims to optimize drugs and regimes of registered and re-purposed anti-wolbachial macrofilaricidal drugs selected from A∙WOL I screening outputs and test these in combination with standard anti-filarial drugs (SAFD). Optimal drugs and regimes will be determined using PK/PD analysis and modelling. The goal is to determine whether these outputs can shorten treatment time to a 7-day treatment duration or less.
Turning the Worm Against its Symbiont – This project will identify new drugs for treating filariasis by developing a screening strategy based on the model nematode Caenorhabditis elegans, and by searching for compounds that can induce an intracellular degradation mechanism known as autophagy to activate the parasite’s immune system and thereby eliminate the resident Wolbachia. This alternative approach should dramatically reduce the time needed to treat lymphatic filariasis compared to current antibiotic-based treatments, which directly target Wolbachia, require long-term administration, and can lead to the development of resistance.
A Small Animal Model Of Onchocerciasis –Treatment options for filarial infections are currently limited and lack affectivity, thus, models of filarial worm infections are invaluable both as a source of worms from all life cycle stages for drug screening, and for preclinical testing of candidate drugs. Dr Joseph Turner and his research team at the Liverpool School of Tropical Medicine will manipulate immune responses mediating resistance to experimental infection to achieve this.
A Cell-Based Screen for Discovery of a Macrofilaricide – Dr Kelly Johnston and her research team at the Liverpool School of Tropical Medicine will develop a parasitic filarial nematode worm cell line that can proliferate continuously in vitro to enable high-throughput screening of candidate anti-filarial drugs. Current drug screening efforts are limited by the complex life cycle of the worms and the difficulties of obtaining sufficient worm numbers. Dr Johnston will isolate worm cells from various life cycle stages and use a high-content screening approach to monitor thousands of cells cultured under different conditions to increase the probability of detecting a stably growing cell line. Once one or more stable cell lines have been produced, they will establish optimal culture conditions for drug screening assays.
A·WOL-Eisai – Researchers will aim to identify and develop new drug candidates that efficiently kill the intracellular bacteria Wolbachia. Funded by GHIT, the most promising drug candidates will proceed through advanced rounds of chemical modification and testing to identify lead candidate compounds that have a good safety and efficacy profiles ready to move into pre-clinical testing.