Why hasn't there been more progress in new Chagas disease drug discovery?

Introduction: Chagas disease (CD) is a neglected disease caused by the protozoan parasite Trypanosoma cruzi. In terms of novel drug discovery, there has been no progress since the 1960s with the same two drugs, benznidazole and nifurtimox, still in use. The complex life cycle, genetic diversity of T. cruzi strains, different sensitivities to the available drugs, as well as little interest from pharmaceutical companies and inadequate methodologies for translating in vitro and in vivo findings to the discovery of new drugs have all contributed to the lack of progress.Areas covered: In this perspective, the authors give discussion to the relevant points connected to the lack of developments in CD drug discovery and provide their expert perspectives.Expert opinion: There are few drugs currently in the preclinical pipeline for the treatment of CD. Only three classes of compounds have been shown to achieve high cure rates in mouse models of infection: nitroimidazoles (fexinidazole), oxaborole DNDi-6148 and proteasome inhibitors (GNF6702). New biomarkers for Chagas' disease are urgently needed for the diagnosis and detection of cure/treatment efficacy. Efforts from academia and pharmaceutical companies are in progress and more intense interaction to accelerate the process of new drugs development is necessary.