Chagas Translation

 

  • Target disease: Chagas
  • Main partners (since project start): Texas Biomedical Research, USA; University of Georgia Research Foundation, USA; McGill University, Canada; London School of Hygiene and Tropical Medicine, UK; CEA/Leti, France; Médecins Sans Frontières; Universidad Mayor de San Simon, Bolivia; Universidad Autónoma Juan Misael Saracho, Bolivia; Barcelona Centre for International Health Research, Spain; Dr Mario Fatala Chaben National Institute of Parasitology, Argentina; University of Texas at El Paso, USA; National Council of Scientific and Technological Research (INGEBI-CONICET), Argentina; University Hospitals of Geneva, Switzerland; NHEPACHA network; Universidad San Martin, Argentina.
  • Project start: 2010
  • Funding (since project start): Department for International Development (DFID), UK; Dutch Ministry of Foreign Affairs (DGIS), the Netherlands; Médecins Sans Frontières/Doctors without Borders, International; Ministry of Health, Brazil; Spanish Agency for International Development Cooperation (AECID), Spain; Swiss Agency for Development and Cooperation (SDC), Switzerland; Wellcome Trust, UK; Other private foundations and individuals.

 

Overall Objective:

  • To identify and evaluate new biological markers of therapeutic efficacy in chronic Chagas disease.

 

  • DNDi received a USD 3 million Strategic Translation Award from the Wellcome Trust to find biomarkers for potential test of cure for Chagas disease [Read Press Release].

 

DNDi has been seeking to identify and/or evaluate biomarkers of therapeutic response to treatment, as the only measurable outcomes to date have been clinical benefit and seroconversion, and, with the exception of children, the latter can take several decades. The initial focus has been on optimizing blood sampling procedures and validation of DNA quantification through polymerase chain reaction (PCR), one of the key outcome measures in use for clinical trials in Chagas disease. The assessment of proteomic signatures in serum samples from nifurtimox-treated Chagas patients previously led to the identification of possible biological markers of therapeutic response. Children show faster seroconversion than adults.

Pre-clinical studies are ongoing to identify and validate potential biological markers of therapeutic response in Chagas disease patients to support clinical development.  In addition, DNDi is fostering and encouraging work for testing four biomarkers to assess response of treatment of Chagas through the Iberoamerican network NHEPACHA.
Analysis of sera from children treated with benznidazole was undertaken in order to evaluate a potential correlation between seroconversion and the presence or absence of biological markers. Early indications are that these can be used to classify patients as cured or not, and results of confirmatory experiments are expected in 2016.

DNDi is collaborating with the University of Georgia and the Texas Biomedical Research Institute in a Wellcome Trust funded, non-human primate study in naturally infected animals with chronic Chagas disease, to further determine PCR and other markers as sensitive tools to consistently differentiate parasitological cure from treatment failure. The dosing period of the non-human primate study in naturally infected animals with chronic Chagas disease ended in 2015, and a 12-month follow-up assessment was completed in August 2015. The study immunosuppression phase was initiated in October 2015 and will end in mid-2016, at which point blood and tissue sample PCR and assessment of other biomarkers will be undertaken to determine if they can differentiate parasitological cure from treatment failure.

DNDi is a member of the NHEPACHA network of investigators created for the long-term cohort evaluation of potential biomarkers.

 

Last update: February 2017