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<p>Infections with the protozoan parasite <i>Trypanosoma cruzi</i> 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.</p>

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Overcoming Trypanosoma cruzi persistence with a mechanistically distinct drug combination

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月30日

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  • Amanda Fortes Francisco,
  • Francisco Olmo,
  • Fanny Escudié,
  • Eric Chatelain,
  • John M. Kelly

摘要

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.