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Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery

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....

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Autores principales: de Araujo, Fernanda Fortes, Nagarkatti, Rana, Gupta, Charu, Marino, Ana Paula, Debrabant, Alain
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287562/
https://www.ncbi.nlm.nih.gov/pubmed/25569299
http://dx.doi.org/10.1371/journal.pntd.0003451
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author de Araujo, Fernanda Fortes
Nagarkatti, Rana
Gupta, Charu
Marino, Ana Paula
Debrabant, Alain
author_facet de Araujo, Fernanda Fortes
Nagarkatti, Rana
Gupta, Charu
Marino, Ana Paula
Debrabant, Alain
author_sort de Araujo, Fernanda Fortes
collection PubMed
description 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.
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spelling pubmed-42875622015-01-12 Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery de Araujo, Fernanda Fortes Nagarkatti, Rana Gupta, Charu Marino, Ana Paula Debrabant, Alain PLoS Negl Trop Dis Research Article 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. Public Library of Science 2015-01-08 /pmc/articles/PMC4287562/ /pubmed/25569299 http://dx.doi.org/10.1371/journal.pntd.0003451 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open-access article distributed under the terms of the Creative Commons Public Domain declaration, which stipulates that, once placed in the public domain, this work may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.
spellingShingle Research Article
de Araujo, Fernanda Fortes
Nagarkatti, Rana
Gupta, Charu
Marino, Ana Paula
Debrabant, Alain
Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery
title Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery
title_full Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery
title_fullStr Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery
title_full_unstemmed Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery
title_short Aptamer-Based Detection of Disease Biomarkers in Mouse Models for Chagas Drug Discovery
title_sort aptamer-based detection of disease biomarkers in mouse models for chagas drug discovery
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4287562/
https://www.ncbi.nlm.nih.gov/pubmed/25569299
http://dx.doi.org/10.1371/journal.pntd.0003451
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