Date: 10 October 2025
Time: 11:00-13:00
Location: ZOOM & Sala Fraga de Azevedo | IHMT-NOVA
Chagas disease, caused by Trypanosoma cruzi, remains a pressing global health challenge. Once confined mainly to Central and South America, its geographic range has expanded, with increasing numbers of cases now reported in North America, Europe, Oceania, and Asia. An estimated 6–7 million people worldwide are currently infected. Despite this burden, there are no vaccines, and treatment relies solely on two nitroheterocyclic drugs, nifurtimox and benznidazole. Both are limited by severe side effects and their dependence on parasite bioactivation by type II nitroreductase, raising risks of cross-resistance and treatment failure. Safer, more effective therapies are urgently needed.
Achieving a complete parasitological cure is essential to prevent chronic disease. However, many small-molecule candidates fail to fully eradicate T. cruzi, allowing parasite persistence and relapse. The clinical failure of CYP51 inhibitors exemplifies this limitation. In addition, parasite population heterogeneity — including dormant subpopulations — reduces susceptibility and complicates treatment. Identifying compounds with the potential for a sterile cure has also been constrained by current in vitro models. Although compound washout assays provide better predictions of regrowth after drug removal, they are low-throughput and require months of incubation, making them impractical for early-stage discovery.
To address this bottleneck, we have developed a high-throughput, rapid screening cascade designed to prioritize compounds with mechanisms of action more likely to achieve sterile cure. At the core of this strategy is a novel high-throughput rate-of-kill (HT-RoK) assay, which monitors the decline of luciferase signal from intracellular T. cruzi amastigotes over five days across varying drug concentrations. This platform enables fast, cost-effective, and scalable evaluation of both time- and dose-dependent activity, allowing early elimination of suboptimal candidates.
By shifting attrition earlier in the discovery pipeline, HT-RoK profiling minimizes late-stage failures and concentrates resources on the most promising drug candidates. This approach has strong potential to accelerate Chagas disease drug discovery and improve translational outcomes.
About Daniel Inaoka
Prof. Daniel Ken Inaoka is Professor at the Institute of Tropical Medicine (NEKKEN), Nagasaki University, where he leads the Department of Molecular Infection Dynamics. Trained in Brazil and Japan, he specializes in parasite biochemistry, mitochondrial energy metabolism, and structural biology, with a strong focus on discovering and validating novel drug targets against parasitic diseases such as Chagas disease and malaria. His research has been pivotal in revealing parasite-specific metabolic pathways and designing inhibitors with therapeutic potential.
With a career spanning the University of Tokyo and Nagasaki University, Prof. Inaoka has combined fundamental biochemical research with translational drug discovery, including collaborative projects with industry partners. He has received multiple international awards for his scientific contributions and is widely published in the fields of molecular parasitology and tropical medicine.
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