A framework for assessing the risk of resistance for anti-malarials in development

Malaria Journal

Methodology

Xavier C Ding¹  Timothy NC Wells¹  David Ubben¹ 

[1] Medicines for Malaria Venture, 20 rte de Pré Bois, CH 1215, Geneva, Switzerland;

关键词: Resistance;    P. falciparum;    Drug development;    Risk assessment;   

DOI  :  10.1186/1475-2875-11-292

 received in 2012-06-07, accepted in 2012-08-01,  发布年份 2012

来源: Springer

【 摘 要 】

Resistance is a constant challenge for anti-infective drug development. Since they kill sensitive organisms, anti-infective agents are bound to exert an evolutionary pressure toward the emergence and spread of resistance mechanisms, if such resistance can arise by stochastic mutation events. New classes of medicines under development must be designed or selected to stay ahead in this vicious circle of resistance control. This involves both circumventing existing resistance mechanisms and selecting molecules which are resilient against the development and spread of resistance. Cell-based screening methods have led to a renaissance of new classes of anti-malarial medicines, offering us the potential to select and modify molecules based on their resistance potential. To that end, a standardized in vitro methodology to assess quantitatively these characteristics in Plasmodium falciparum during the early phases of the drug development process has been developed and is presented here. It allows the identification of anti-malarial compounds with overt resistance risks and the prioritization of the most robust ones. The integration of this strategy in later stages of development, registration, and deployment is also discussed.

【 授权许可】

CC BY   
© Ding et al.; licensee BioMed Central Ltd. 2012