Emerging agents for the treatment of Chagas disease: what is in the preclinical and clinical development pipeline?

Abstract

INTRODUCTION:

Chagas disease treatment relies on the lengthy administration of benznidazole and/or nifurtimox, which have frequent toxicity associated. The disease, caused by the parasite Trypanosoma cruzi, is mostly diagnosed at its chronic phase when life-threatening symptomatology manifest in approximately 30% of those infected. Considering that both available drugs have variable efficacy by then, and there are over 6 million people infected, there is a pressing need to find safer, more efficacious drugs.

AREAS COVERED:

We provide an updated view of the path to achieve the aforementioned goal. From state-of-the-art in vitro and in vivo assays based on genetically engineered parasites that have allowed high throughput screenings of large chemical collections, to the unfulfilled requirement of having treatment-response biomarkers for the clinical evaluation of drugs. In between, we describe the most promising pre-clinical hits and the landscape of clinical trials with new drugs or new regimens of existing ones. Moreover, the use of monkey models to reduce the pre-clinical to clinical attrition rate is discussed.

EXPERT OPINION:

In addition to the necessary research on new drugs and much awaited biomarkers of treatment efficacy, a key step will be to generalize access to diagnosis and treatment and maximize efforts to impede transmission.

• Authors: Nieves Martínez-Peinado, Nuria Cortes-Serra, Irene Losada-Galvan, Cristina Alonso-Vega, Julio A Urbina, Ana Rodríguez, John L VandeBerg, Maria-Jesus Pinazo, Joaquim Gascon, Julio Alonso-Padilla
• Journal: Expert opinion on investigational drugs (Expert Opin Investig Drugs) Vol. 29 Issue 9 Pg. 947-959 (Sep 2020) ISSN: 1744-7658 [Electronic] England
• PMID: 32635780 (Publication Type: Journal Article, Review)

Chemical References

• Trypanocidal Agents

Topics

• Animals
• Chagas Disease (diagnosis, drug therapy, parasitology)
• Disease Models, Animal
• Drug Development
• Haplorhini
• High-Throughput Screening Assays
• Humans
• Trypanocidal Agents (adverse effects, pharmacology)
• Trypanosoma cruzi (isolation & purification)