Chagas Translational platform 

Despite significant progress in Chagas disease drug discovery, current treatment options remain limited to benznidazole and nifurtimox, both of which are associated with lengthy treatment regimens, suboptimal efficacy in some patient populations, and potential tolerability challenges. An important obstacle to achieving consistent parasitological cure is the ability of a small sub-population of Trypanosoma cruzi parasites to survive drug exposure. Growing evidence suggests that these drug-tolerant, quiescent parasites may contribute to treatment failure and disease persistence, highlighting the need for innovative therapeutic strategies capable of overcoming this challenge.

Recent studies have generated important insights into both the biology of parasite persistence and the potential of novel therapeutic approaches. Building on this work, the proposed research will further investigate the molecular mechanisms associated with quiescent and drug-tolerant T. cruzi populations through the characterization of their phenotypic, transcriptomic, and proteomic profiles. These studies aim to identify pathways, targets, and biomarkers associated with parasite persistence that could be leveraged to improve drug discovery efforts, refine screening cascades, and support the development of new therapeutic interventions.

In parallel, the project will explore combination treatment strategies designed to enhance treatment efficacy and overcome parasite persistence. Building on encouraging pre-clinical findings demonstrating the potential benefit of combining benznidazole with novel anti-T. cruzi compounds, the programme will evaluate rational drug combinations that may deliver greater efficacy, reduced treatment duration, and improved tolerability compared with current treatment approaches.

Together, these complementary activities seek to address two critical barriers in Chagas disease drug development – parasite persistence and treatment failure – to create new opportunities for the development of transformative therapies capable of delivering more reliable, durable cures.