title: Aptamer-based detection of disease biomarkers in mouse models for chagas drug discovery.
abstract: Drug discovery initiatives, aimed at Chagas treatment, have been hampered by the lack of standardized drug screening protocols and the absence of simple pre-clinical assays to evaluate treatment efficacy in animal models. In this study, we used a simple Enzyme Linked Aptamer (ELA) assay to detect T. cruzi biomarker in blood and validate murine drug discovery models of Chagas disease. In two mice models, Apt-29 ELA assay demonstrated that biomarker levels were significantly higher in the infected group compared to the control group, and upon Benznidazole treatment, their levels reduced. However, biomarker levels in the infected treated group did not reduce to those seen in the non-infected treated group, with 100% of the mice above the assay cutoff, suggesting that parasitemia was reduced but cure was not achieved. The ELA assay was capable of detecting circulating biomarkers in mice infected with various strains of T. cruzi parasites. Our results showed that the ELA assay could detect residual parasitemia in treated mice by providing an overall picture of the infection in the host. They suggest that the ELA assay can be used in drug discovery applications to assess treatment efficacy in-vivo.
authors.affiliation: Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Fernanda Fortes
authors.initials: FF
authors.lastname: de Araujo
authors.affiliation: Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Rana
authors.initials: R
authors.lastname: Nagarkatti
authors.affiliation: Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Charu
authors.initials: C
authors.lastname: Gupta
authors.affiliation: Molecular Signaling Section, Laboratory of Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, United States of America.
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Marino
authors.affiliation: Laboratory of Emerging Pathogens, Division of Emerging and Transfusion Transmitted Diseases, Center for Biologics Evaluation and Research, United States Food and Drug Administration, Silver Spring, Maryland, United States of America.
authors.forename: Alain
authors.initials: A
authors.lastname: Debrabant
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D052157:Aptamers, Nucleotide; D001483:Base Sequence; D015415:Biomarkers; D014355:Chagas Disease / Q000188:drug therapy*; D005260:Female; D005786:Gene Expression Regulation; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009593:Nitroimidazoles / Q000494:pharmacology; D012313:RNA / Q000235:genetics / Q000378:metabolism
chemical_list: D000981:Antiprotozoal Agents; D052157:Aptamers, Nucleotide; D015415:Biomarkers; D009593:Nitroimidazoles; D012313:RNA; C009999:benzonidazole