Title:Challenges in Chagas Disease Drug Discovery: A Review
Volume: 23
Issue: 28
Author(s): Rocio Paucar, Elsa Moreno-Viguri and Silvia Pérez-Silanes
Affiliation:
Keywords:
Chagas disease, Trypanosoma cruzi, drug discovery, screening cascade, clinical trials, target product
profile, neglected tropical disease.
Abstract: Chagas disease or American trypanosomiasis is a neglected
tropical disease caused by the parasite Trypanosoma cruzi. Although the
number of infected individuals has decreased, about 6-7 million people are
infected worldwide. The chemotherapy drugs currently used are limited to
benznidazole and nifurtimox. They are effective in acute phase, congenital
transmission and children with chronic infection; however, recent clinical
trials have shown limitations in adults with chronic infection, presenting
drawbacks during the treatment. Thus, there is an urgent need for new effective,
safe and affordable drugs to fight against this complex disease. There
were high expectations for azole derivatives as they appeared to be the most
promising drugs for the treatment of Chagas disease during the last decade; however, the
disappointing results obtained so far in clinical trials evidenced the lack of correlation between
preclinical and clinical development. Therefore, the feedback obtained from these
studies should define the starting point for addressing a roadmap for the drug discovery
process in the fight against this disease. To tackle this challenge, it is important to keep in
mind the drug target profile, already defined by panels of experts, and the coordinated work
involving multi-disciplinary networks focusing not only on the discovery of new drugs but
also on the standardization of the protocols that would allow acceleration in the Chagas disease
drug discovery process.
