Animal models of Chagas disease and their translational value to drug development

Expert Opin Drug Discov. 2020 Dec;15(12):1381-1402. doi: 10.1080/17460441.2020.1806233. Epub 2020 Aug 19.

Abstract

Introduction: American trypanosomiasis, better known as Chagas disease, is a global public health issue. Current treatments targeting the causative parasite, Trypanosoma cruzi, are limited to two old nitroheterocyclic compounds; new, safer drugs are needed. New tools to identify compounds suitable for parasitological cure in humans have emerged through efforts in drug discovery.

Areas covered: Animal disease models are an integral part of the drug discovery process. There are numerous experimental models of Chagas disease described and in use; rather than going through each of these and their specific features, the authors focus on developments in recent years, in particular the imaging technologies that have dramatically changed the Chagas R&D landscape, and provide a critical view on their value and limitations for moving compounds forward into further development.

Expert opinion: The application of new technological advances to the field of drug development for Chagas disease has led to the implementation of new and robust/standardized in vivo models that contributed to a better understanding of host/parasite interactions. These new models should also build confidence in their translational value for moving compounds forward into clinical development.

Keywords: Trypanosoma cruzi; in vivo; Bioluminescence; imaging; parasitological cure; pharmacokinetic/pharmacodynamic relationships; predictability.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Chagas Disease / drug therapy*
  • Chagas Disease / parasitology
  • Disease Models, Animal
  • Drug Development*
  • Drug Discovery
  • Host-Parasite Interactions
  • Humans
  • Trypanocidal Agents / administration & dosage*
  • Trypanocidal Agents / adverse effects
  • Trypanocidal Agents / pharmacology
  • Trypanosoma cruzi / isolation & purification

Substances

  • Trypanocidal Agents