Short-course combination treatment for experimental chronic Chagas disease

By González S, Wall R J, Thomas J, Braillard S, Brunori G, Camino Díaz I, Cantizani J, Carvalho S, Castañeda Casado P, Chatelain E, Cotillo I, Fiandor JM, Francisco AF, Grimsditch D, Keenan M, Kelly JM, Kessler A, Luise C, Lyon JJ, MacLean L, Marco M, Martin JJ, Martinez Martinez MS, Paterson C, Read KD, Santos-Villarejo A, Zuccotto F, Wyllie S, Miles TJ, De Rycker M. Science Translational Medicine 2023, 15(726). doi: 10.1126/scitranslmed.adg8105

Summary: Chagas disease, a neglected tropical disease caused by the protozoan parasite Trypanosoma cruzi, kills more people in Latin America each year than any other parasitic disease, including malaria. Current treatments have limited efficacy, are lengthy, and often lead to adverse side effects. Better, shorter treatment options are urgently needed for the more than 6 million people with Chagas in the world. In this paper, authors describe a highly selective and efficacious lead compound in the pyrrolopyrimidine series that offers a promising opportunity to improve on current treatments. The combination of the lead pyrrolopyrimidine compound with a sub-efficacious dose of benznidazole rapidly cleared T. cruzi parasites, both in vitro and in vivo, showing great potential to overcome key issues associated with currently available treatments and offering the prospect of safer and shorter treatment regimens.

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