Chagas Translation

 

  • Target disease: Chagas
  • Main Partners (since project start): Abbvie, USA; Anacor Pharmaceuticals Inc., USA; Centre for Drug Candidate Optimization, Monash University, Australia; Epichem, Australia; Fundaçao de Apoio Universidade Federale de Sao Paolo (FapUnifesp), USP São Carlos, Brazil; Griffith University, Australia; Institut Pasteur Korea (IPK), Korea; Laboratory of Microbiology, Parasitology and Hygiene, Antwerp University, Belgium; London School of Hygiene and Tropical Medicine, UK; LNBio/CNPEM, Brazil; Murdoch University, Australia; Sandexis, UK; Sanofi, France; University of Campinas, Brazil; TGC Lifesciences, India; WuXi AppTec, China.
  • Project start: 2008
  • Funding (since project start): Brazilian Development Bank (BNDES), Brazil; Department for International Development (DFID), UK; FIOTEC, Brazil; Médecins Sans Frontières/Doctors without Borders; Ministry of Health, Brazil; Swiss Agency for Development and Cooperation (SDC), Switzerland.

 

Overall Objective:

  • Optimize leads issued from Hit-to-Lead series and identify pre-clinical candidates with the potential to fulfill the target product profile (TPP).

 

Current therapy for Chagas disease is limited to two nitroheterocyclic drugs, nifurtimox and benznidazole. Although these drugs are associated with a substantial amount of side-effects that can limit their use, recent controlled clinical trials have shown potential for parasitological cure (as assessed by the lack of parasite rebound following one year follow-up) in up to 90% of chronic indeterminate Chagas patients.

However, in order to guarantee a robust pipeline for new drug candidates for patients with chronic Chagas disease, it is important to continue a lead optimization strategy exploring a range of chemical scaffolds. Efforts are being made to identify new leads series from current ongoing Hit-to-Lead activities by taking advantage of screening platforms against T. cruzi. Promising in vivo Chagas models using bioluminescent imaging developed with LSHTM are now part of the screening cascade.

Two new compounds issued from two new chemical classes showed curative activities against chronic infection in the bioluminescence imaging mouse model. It was the first time that non-nitroimidazoles compounds have been found to be curative in this model.


Last update: February 2017