- Target disease: Chagas
- Main Partners (since project start): Abbvie, USA; Anacor Pharmaceuticals Inc., USA; Celgene Corporation, USA; Centre for Drug Candidate Optimization, Monash University, Australia; Drug Discovery Unit, University of Dundee, UK; Epichem, Australia; Fundaçao de Apoio Universidade Federale de Sao Paolo (FapUnifesp), USP São Carlos, Brazil; Eskitis Institute for Cell and Molecular Therapies, Griffith Institute for Drug Discovery, Australia; GlaxoSmithKline, UK; Griffith University, Australia; Institut Pasteur Korea (IPK), Korea; Laboratory of Microbiology, Parasitology and Hygiene, Antwerp University, Belgium; London School of Hygiene & 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.
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 of Chagas disease in a bioluminescence imaging mouse model developed by the London School of Hygiene & Tropical Medicine. It was the first time that non-nitroimidazoles compounds have been found to be curative in this model.
Last update: March 2018