Discovering and developing novel therapeutics for Chagas disease

• Grant number: 24/14603-3
• Support Opportunities: Research Grants - Visiting Researcher Grant - International
• Start date: April 28, 2025
• End date: June 13, 2025
• Field of knowledge: Biological Sciences - Parasitology - Protozoology of Parasites
• Principal Investigator: Ariel Mariano Silber
• Grantee: Ariel Mariano Silber
• Visiting researcher: Maria Belen Cassera
• Visiting researcher institution: University of Georgia, Athens (UGA), United States
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 21/12938-0 - Amino acid metabolism in Trypanosoma cruzi: a toolbox to survive in hostile environments, AP.TEM

Abstract

Chagas disease has become a worldwide challenge that can have severe consequences for human health over the long term. It is caused by the Trypanosoma cruzi parasite, and it can be acquired by vector transmission, through blood, and organ donors and from mother to child. Two drugs introduced more than 40 years ago, nifurtimox and benznidazole, are the only options approved for treatment, particularly during the acute phase. However, both compounds exhibit significant side effects, leading to poor adherence in long treatments as required during the chronic phase. Thus, there is an urgent need for new and more-effective drugs to treat Chagas disease and this must be achieved in a cost-effective manner to deliver drugs that are safe, effective, affordable, and available to those who need them most. Moreover, there is a critical need to identify novel trypanocidal compounds effective across all disease stages. Over the years, synthetic compounds inspired by indole alkaloids have been investigated for their trypanocidal potential. This research project focuses on identifying new chemical scaffolds with anti-trypanosome activity using a proprietary compound library of novel tetrahydro-¿-carbolines, ¿-carbolines, and other indole alkaloids as a starting point for the development of novel therapies for Chagas disease. The potential trypanocidal activity of this collection of unique compounds will be assessed against critical stages of the infection, including intracellular replicating and non-replicating amastigotes. This collaboration leverages the complementary knowledge and expertise of both research groups. The ultimate goal is to develop a novel treatment for Chagas disease that could be developed through a collaboration between the United States and Brazil. (AU)