A drug candidate that can rid mice of the parasites that cause Chagas disease, leishmaniasis and sleeping sickness is reported online in Nature this week. The research suggests that a single class of drugs could be used to treat these multiple, neglected diseases, which collectively lead to more than 50,000 human deaths annually.
Chagas disease, leishmaniasis and sleeping sickness affect 20 million people worldwide, primarily in poor communities in Latin America, Asia and Africa. The three diseases are caused by three similar parasites, so Frantisek Supek and colleagues sought to identify a shared protein that could be targeted by a single drug class. From a starting list of over 3 million contenders, they identified one promising compound then refined its chemical structure further to increase its potency and bioavailability.
The drug candidate, named GNF6702, performed well in mouse models of the three diseases, where it appears to work by selectively blocking the activity of the parasite proteasome, a tiny structure involved in protein regulation. Although treatments for Chagas disease, leishmaniasis and sleeping sickness exist, they are expensive, poorly tolerated and of limited effect. The new compound, in contrast, was well tolerated by mice and appears not to disturb the normal functioning of mammalian cells.
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