Overcoming Trypanosoma cruzi persistence with a mechanistically distinct drug combination

Abstract Infections with the protozoan parasite Trypanosoma cruzi are widespread in the Americas and can lead to severe cardiac and/or gastrointestinal pathology. Current treatments are limited to monotherapies characterised by prolonged dosing regimens, disputed efficacy and toxic side-effects. Sterile cure is often confounded by persistence of a small sub-population of parasites that display increased drug tolerance. Here, we demonstrate that short duration co-administration of well-tolerated sub-efficacious oral doses of the parasite-selective proteasome inhibitor GNF6702 and the pro-drug benznidazole produce parasitological cure in an experimental model of chronic Chagas disease.