Mahidol University

Start : June 2015 | Status : Complete

The scientist: Dr. Krittikorn Kumpornsin will focus her research on the identification of new chemical entities efficacious against natural P. falciparum isolates from the patients with delayed parasitic clearance to artemisinin treatments through a project titled “Reversal of Artemisinin Resistance by means of Chemical Genetics”. Her work will contribute to tackle the emerging issue of decreased efficacy of current gold-standard antimalarial treatments, including artemisinin-combination therapies (ACTs).  Krittikorn is a biochemist by training. She obtained her bachelor degree in Microbiology from Srinakharinwirot University (Thailand). She worked at the Division of Molecular Genetics, Siriraj Hospital and then at the department of Biochemistry, Mahidol University. Krittikorn obtained her Ph.D. in Biochemistry in 2014 from the University of Mahidol (Thailand) and has an extensive experience in malaria biochemistry and drug resistance.

The sponsors:  Dr. Chookajorn’s laboratory at the Faculty of Tropical Medicine at Mahidol University based in Thailand is tackling the problems of malaria drug resistance and pathogenesis using molecular biology and evolutionary biology approaches. The drug resistance research they have conducted has been focused on the genetic interactions that affect the evolutionary course of gaining new resistant phenotypes. They take advantage of their privileged location in the drug-resistant hotspot of the Greater Mekong Subregion, which led in the past to their contributions to antifolate resistance evolution studies. Their location strategically allows direct access to field resources, such as patient isolates with a delayed response to current gold-standard antimalarial treatments (ACTs) and local experts.

Foundation funding: The Foundation is providing £84,212 in support.

GSK’s contribution: GSK will allocate in-kind contribution to the project, including extensive screening exercise and drug discovery mentoring. GSK will provide access to Biosafety Level 3 facilities to conduct in vitro malaria studies and to GSK´s collection of compounds for screening campaigns.

Project Description: Artemisinin is an effective drug used for the treatment of Plasmodium falciparum malaria. The drug can quickly clear the parasites from the patients because of its broad activity against every stage within human red blood cells. Despite its effectiveness in saving lives, the target of artemisinin is not yet identified, preventing the possibility of exploiting a similar inhibitory mechanism for drug development. The lack of understanding has become a pressing issue now more than ever because of the rise in artemisinin resistance in Southeast Asia.  It has been reported that certain oxidizing agents have the potential to moderately modulate the sensitivity level of artemisinin. This observation suggests the possibility that the effect of artemisinin on parasites could be manipulated by chemical compounds. The plan is to screen for compounds that can overcome artemisinin resistance, by “resensitizing” artemisinin-resistant parasites from patients with delayed clearance. The putative compounds are likely to interfere with the target of artemisinin or resistance mechanism.  The innovation of the project proposal comes from the use of natural P.falciparum isolates from the patients with delayed parasite clearance by artemisinin that have been adapted for in vitro culture. These natural isolates provide a unique resource for screening purposes. The proposed duration of the project is 15 months and will involve a close collaboration between the University of Mahidol and GSK Medicine Development Campus at Tres Cantos.