River blindness and elephantiasis are 2 of the leading causes of global disability.
A new anti-Wolbachia drug will now be investigated as a treatment for onchocerciasis (river blindness) and lymphatic filariasis (elephantiasis), according to a recent report.
Both onchocerciasis and lymphatic filariasis are neglected tropical diseases that affect more than 157 million people worldwide, making them prime candidates for the therapy. They are 2 of the leading causes of global disability.
However, in the US, individuals cannot get infected with lymphatic filariasis, and onchocerciasis infections are few and far between, according to the Centers for Disease Control and Prevention (CDC).
Investigators from the Liverpool School of Tropical Medicine and the University of Liverpool found their starting point through the A-WOL program funded by the Bill and Melinda Gates Foundation, which works on anti-Wolbachia screenings. The novel synthetic drug called AWZ1066S treats Wolbachia, a bacterial symbiont that parasites need for survival.
“The anti-Wolbachia strategy has proved to be a paradigm changing therapeutic approach to treatment,” study author Mark Taylor, PhD, said in a press release. “The further development of AWZ1066S represents another step forward in bringing relief to many millions of people.”
The drug is designed to have minimal impact on the gut microbiota. Other anti-Wolbachia treatments are broad spectrum antibiotics, and patients can develop resistance. AWZ1066S has a faster kill rate compared to other such antibiotics tested against Wolbachia, the investigators. They believe this suggests that the treatment time frame could be under 7 days.
There are anti-filarial drugs, such as doxycycline, but they are not widely available or generally considered safe, the study authors wrote.
“The novel synthetic molecule, AWZ1066S, was designed and developed at Liverpool from screening hits, and involved multi-parameter chemical optimization with evaluation of over 400 analogues,” co-senior author Paul O’Neill, PhD, added in the statement. “Our approach has provided a molecule with high potency and specificity against the target pathogen along with desired oral drug properties.”
Previous proof-of-concept human trials showed that depleting Wolbachia using antibiotics may lead to safe outcomes. With AWZ1066S, a highly-specific anti-Wolbachia drug, the investigators targeted particular efficacy, safety, and drug metabolism/pharmacokinetic features. Because of its successful testing in preclinical models of infection, the potential treatment shows promise, the authors noted. It also has drug metabolism/pharmacokinetic properties that are compatible with a 7-days-or-less oral therapy.
The drug was created in partnership with Eisai Ltd and AstraZeneca. This support “enabled development of this drug in a very short time frame,” O’Neill said.
The team’s next step is to use this drug in formal preclinical evaluations. If the predicted results can be confirmed in clinical trials, the investigators believe if will provide a unique opportunity to significantly contribute to communities affected by filariasis in order to eliminate onchocerciasis and lymphatic filariasis.
“This first-in-class and highly potent and specific anti-Wolbachia preclinical candidate molecule, AWZ1066S, has the potential to significantly impact current global onchocerciasis and lymphatic filariasis elimination programs and reduce elimination time frames from decades to years,” the study authors concluded.
The paper, titled “AWZ1066S, a highly specific anti-Wolbachia drug candidate for a short-course treatment of filariasis,” was published in the journal Proceedings of the National Academy of Sciences.