A novel way to end sleeping sickness by making a parasite that causes it to self-destruct has been discovered by scientists from Vanderbilt University.
They have identified an enzyme that protects the protozoa that cause sleeping sickness, Chagas disease and leishmaniasis, and a compound that appears to obstruct those efforts.
"With human migrations, HIV co-infections and the broadening of the host reservoirs due to climate changes, sleeping sickness and other diseases caused by these protozoan pathogens are now spreading around the world, including within the United States and Europe," said Vanderbilt University scientist Galina Lepesheva.
"It is our hope that the results of our work might be helpful for the development of an effective treatment for such protozoan infections, some of which still remain incurable," Lepesheva added.
Lepesheva and her team have focussed their research on trypanosomatidae family of parasites.
"It has been known for some time that T. brucei, the parasite that causes sleeping sickness, consumes cholesterol in its human host's blood to shore up the cellular membrane, and researchers presumed there was no getting around that," said Lepesheva.
"But we suspected the parasite, like plants and animals, still might need to make its own sterols for growth and development-functional sterols - that could be targeted and inhibited," Lepesheva added.
The team chose to attack the parasite's enzyme known as 14DM,
"We tested hundreds of compounds as potential 14DM inhibitors. One of them, VNI, was one of the best in terms of killing the parasites that cause sleeping sickness, Chagas and Leishmaniasis," she said.
The team named the inhibitor VNI, short for Vienna Novartis Inhibitor, because it originally was synthesized at the Novartis Research Institute in Vienna.
It binds with the worker enzyme and blocks the enzyme's ability of causing sleeping sickness.
The study appears in Journal of Biological Chemistry.