What are the translational challenges associated with Chagas disease drug discovery?

Abstract

Chagas disease is endemic in Latin American countries. However, cases have been found in non-endemic areas such as the United States, Canada, Japan and some countries in Europe and Africa due to population migration. There are still only two drugs to treat this disease used for more than five decades, which are benznidazole (BNZ) and nifurtimox (NFX). These nitroheterocyclic compounds, really are a prodrug whose mechanism of action is still unknown. They are effective in the acute phase with a long treatment period, during which they produce adverse effects that cause 10–30% of patients to abandon the treatment, and their administration is not recommended during pregnancy or the chronic phase of the disease [Citation2]. Nifurtimox is preferably used for pediatric treatment and more readily available in non-endemic countries. Thus, the identification of new effective and safe therapeutic options continues to be one of the main lines of research against Chagas disease, however there are challenges that affect its progress. In this search for effective therapeutic options, it is essential to consider the biological and genetic characteristics of Trypanosoma cruzi parasite, etiological agent of Chagas disease. These peculiarities of the parasite are related to variations in the susceptibility to treatment, clinical manifestations, evasion of the host immune response, and the parasite’s ability to be found in different media such as blood or organs and in different forms. In this opinion article, we consider that the challenges in Chagas disease research and treatment requires a concerted effort to bridge the gap between laboratory findings and clinical trials, establish standardized protocols, understand parasite variability, and promote interdisciplinary collaboration. These needs are important for developing effective treatments and improving outcomes for patients affected by this silent disease.