Overcoming Trypanosoma cruzi persistence with a mechanistically distinct drug combination

Francisco AF, Olmo F, Escudié F, Chatelain E, Kelly JM. NPJ Antimicrob Resist 2026,4(1):30. doi:10.1038/s44259-026-00205-8

Summary: Infections with 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. The authors of this manuscript demonstrate that short duration co-administration of well-tolerated sub-efficacious oral doses of the parasite-selective proteasome inhibitor GNF6702 (30 mg/kg)  and low doses (10 mg/kg) of the pro-drug benznidazole produce parasitological cure (100%) in an experimental model of chronic Chagas disease, with no adverse side-effects. Combination therapy with these drugs, with distinct modes of action, could represent a promising option for treatment of Chagas disease.

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