Drug innovation may help fight neglected tropical diseases

Neglected tropical diseases affect over 157 million people globally

neglected-tropical-diseases-human-whipworm-Trichuris-trichiura--high-magnification Human whipworm (Trichuris trichiura) female. Permanent slide plate under high magnification

Scientists have developed a novel drug that could be used to treat neglected tropical diseases which can lead to severe disability and affect over 157 million people globally.

The researchers from University of Liverpool in the UK have successfully optimised a hit from a whole cell screening of a 10,000-compound library to deliver the first novel fully synthetic and rationally designed anti-Wolbachia drug, AWZ1066S, which could potentially be used to treat onchocerciasis and lymphatic filariasis (LF).

"The identification represents the first potential designer drug of its kind, specifically targeting Wolbachia as a curative treatment for onchocerciasis and LF," said Steve Ward, a researcher at University of Liverpool in the UK.

"The candidate selection status of this compound represents the successful conclusion to a multidisciplinary teams 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," said Ward, co-senior author of the study published in the journal PNAS.

"Over 157 million people globally are affected by onchocerciasis and LF, this particular molecule has the potential to shorten that timescale of treatments from weeks to days which could significantly impact the international timetable for the elimination of these two neglected tropical diseases," he said.

Onchocerciasis and LF are neglected tropical diseases (NTDs) caused by filarial parasites that can lead to severe disability.

The inability of current drugs to kill adult parasites has highlighted the urgent need for new curative anti-filarial drugs for these debilitating diseases.

In the search for new anti-filarial drugs, researchers have focussed on targeting Wolbachia, a bacterial symbiont that is essential for parasite development and survival.

Although the anti-filarial drug, doxycycline has proven effective clinically through the depletion of Wolbachia, the treatment regimens are protracted, and contradictions restrict its widespread implementation.

AWZ1066S's high specificity is a significant advantage resulting in minimal impact on the gut microbiota, and the selection and emergence of resistance following the administration to patients, unlike other anti-Wolbachia based broad spectrum antibiotic treatments.

It also has a faster kill rate compared to other known antibiotics tested against Wolbachia in vitro suggesting that the time-frame for treatment delivery could be fewer than 7 days.