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Animal models of efficacy to accelerate drug discovery in malaria

Published online by Cambridge University Press:  21 June 2013

MARÍA BELÉN JIMÉNEZ-DÍAZ ,
SARA VIERA ,
ELENA FERNÁNDEZ-ALVARO  and
IÑIGO ANGULO-BARTUREN
MARÍA BELÉN JIMÉNEZ-DÍAZ
Affiliation:
GlaxoSmithKline, Diseases of the Developing World-Tres Cantos Medicines Development Campus, Tres Cantos 28760, Madrid, Spain
SARA VIERA
Affiliation:
GlaxoSmithKline, Diseases of the Developing World-Tres Cantos Medicines Development Campus, Tres Cantos 28760, Madrid, Spain
ELENA FERNÁNDEZ-ALVARO
Affiliation:
GlaxoSmithKline, Diseases of the Developing World-Tres Cantos Medicines Development Campus, Tres Cantos 28760, Madrid, Spain
IÑIGO ANGULO-BARTUREN*
Affiliation:
GlaxoSmithKline, Diseases of the Developing World-Tres Cantos Medicines Development Campus, Tres Cantos 28760, Madrid, Spain
*
*Corresponding author: GlaxoSmithKline, Diseases of The Developing World, Tres Cantos Medicines Development Campus, Severo Ochoa, 2. Tres Cantos 28760, Madrid, Spain. Tel: +34 650 685 404. Fax: +34 91 807 05 95. E-mail: inigo.x.angulo@gsk.com
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Summary

The emergence of resistance to artemisinins and the renewed efforts to eradicate malaria demand the urgent development of new drugs. In this endeavour, the evaluation of efficacy in animal models is often a go/no go decision assay in drug discovery. This important role relies on the capability of animal models to assess the disposition, toxicology and efficacy of drugs in a single test. Although the relative merits of each efficacy model of malaria as human surrogate have been extensively discussed, there are no critical analyses on the use of such models in current drug discovery. In this article, we intend to analyse how efficacy models are used to discover new antimalarial drugs. Our analysis indicates that testing drug efficacy is often the last assay in each discovery stage and the experimental designs utilized are not optimized to expedite decision-making and inform clinical development. In light of this analysis, we propose new ways to accelerate drug discovery using efficacy models.

Keywords

Drug discoverymalariaanimal modelscritical pathhumanised mouse
Type
Research Article
Information
Parasitology , Volume 141 , Issue 1: Symposia of the British Society for Parasitology volume 49 Emerging paradigms in anti-infective drug design , January 2014 , pp. 93 - 103
Copyright
Copyright © Cambridge University Press 2013 

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