A new potential drug molecule could reduce treatment times for two widespread diseases from weeks to days, ultimately helping to eliminate them.
The new molecule has been designed to more effectively target and kill the cause of elephantiasis and river blindness while having potentially fewer side effects.
Reducing treatment times for individuals could also accelerate programs to eliminate the diseases altogether, reducing the timescales from decades to years.
The mechanism we used is completely unique, and by identifying this new target we will reveal new insights into the bacteria-worm symbiosis. Professor Ed Tate
The research team, led by the University of Liverpool and the Liverpool School of Tropical Medicine and including Imperial College London chemists, published details of the molecule this week in Proceedings of the National Academy of Sciences. The molecule will now enter preclinical trials, to determine if it is safe to trial on humans.
Elephantiasis (lymphatic filariasis) causes severe swelling in the arms, legs, breasts or genitals that can become very painful, and river blindness (onchocerciasis) causes severe itching and bumps under the skin, and is the second-most common cause of blindness due to infection. Together they affect 157 million people worldwide.
Both diseases are caused by parasitic worms. There are few existing drugs that can kill the worms, particularly in the adult stage, and those that do require weeks of treatment and can cause side effects or interact with other drugs.
Faster treatment and fewer side effects
The new molecule targets a species of bacteria called Wolbachia that lives within the worms, which in turn live within the human host. The worms rely on this ‘symbiotic’ relationship with the bacteria for their development and survival. By targeting these bacteria very specifically, the molecule is expected to have fewer side effects, for example having less impact on patients’ guts.
The treatment is also expected to work far faster than previous drugs, killing the worms in less than a week, which could also prevent the bacteria becoming resistant to the drugs.
Professor Ed Tate, from Imperial’s Department of Chemistry, is Director of the Centre for Drug Discovery Science and led the work at Imperial. He said: “The mechanism we used is completely unique, and by identifying this new target we will reveal new insights into the bacteria-worm symbiosis. These insights could in turn be exploited to develop still more effective drugs against the worms, or even novel antibiotics to combat antimicrobial resistance in unrelated pathogens.”
Screening 10,000 compounds
To create the drug molecule, the team screened 10,000 compounds looking for candidates that would affect the Wolbachia bacteria. They then took forward several drug designs that balanced efficacy at killing the parasite, human safety and the ability to be easily broken down in the body when taken as an oral drug.
Professor Steve Ward, senior author and Deputy Director of the Liverpool School of Tropical Medicine, said: “The identification represents the first potential designer drug of its kind, specifically targeting Wolbachia as a curative treatment for onchocerciasis and lymphatic filariasis.
“The candidate selection status of this compound represents the successful conclusion to a multidisciplinary team’s efforts to generate the first synthetic drug specifically developed to target this bacteria and we are really excited to take the compound to the next stage of its development.”
The starting point for the work was screening activities of the A.WOL programme funded through the Bill and Melinda Gates Foundation, and the work at Imperial was funded by Collaboration Kick-start Funding by the Faculty of Natural Sciences. The team also partnered with Eisai Ltd, with additional support from AstraZeneca, which allowed the candidate drug molecule to be fast-tracked.
‘AWZ1066S, a highly specific anti-Wolbachia drug candidate for a short-course treatment of filariasis’ by W. David Hong et al. is published in Proceedings of the National Academy of Sciences.
Article text (excluding photos or graphics) © Imperial College London.
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