New Treatments for Chagas Disease

  • Baell, Jonathan (Primary Chief Investigator (PCI))
  • Kelly, John (Chief Investigator (CI))

Project: Research

Project Description

Chagas disease was first described in 1909. Although over a century has passed since its discovery, it remains one of the largest parasitic disease burdens and is described as the most burdensome neglected tropical disease in Latin American countries. An estimated 6 – 7 million people are infected worldwide with approximately 25 million people living at risk of infection. Roughly 220,000 cases and more than 14,000 deaths are reported annually. Vector-borne transmission occurs through the Triatomine bug (also known as the ‘kissing bug’ or ‘assassin beetle’). This insect vector carries and transmits the flagellated protozoan parasite, Trypanosoma cruzi (T. cruzi), which is the causative agent of Chagas disease.

There are currently two chemotherapeutic options for T. cruzi infection; benznidazole and nifurtimox. However, both drugs have attributes that make them less than ideal therapeutics. The side effects of these drugs are often so severe (especially in adults) that the discontinuation of treatment is common and patient compliance is a major issue. Furthermore, the dosing regimen is difficult, (3 tablets a day for approximately 1-3 months), which would be particularly difficult to follow in poorer, rural communities.

We have in hand a small molecule that potently inhibits T.cruzi with a IC50 of 0.24-0.76uM. It is non-cytotoxic to a panel of mammalian cells, it is highly drug-like and it is based on a novel scaffold. In order to translate this probe into a viable drug candidate, we need to improve activity by an order of magnitude and identity sites where modification leads to increased metabolic stability. That is the objective of this research plan.
Short titleNew Treatments for Chagas Disease
StatusActive
Effective start/end date1/01/1931/12/21