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Aptamer-based detection of disease biomarkers in mouse models for chagas drug discovery.

Authors :
de Araujo FF
Nagarkatti R
Gupta C
Marino AP
Debrabant A
Source :
PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2015 Jan 08; Vol. 9 (1), pp. e3451. Date of Electronic Publication: 2015 Jan 08 (Print Publication: 2015).
Publication Year :
2015

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.

Details

Language :
English
ISSN :
1935-2735
Volume :
9
Issue :
1
Database :
MEDLINE
Journal :
PLoS neglected tropical diseases
Publication Type :
Academic Journal
Accession number :
25569299
Full Text :
https://doi.org/10.1371/journal.pntd.0003451