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Molecular models advance the fight against malaria

Research from Dartmouth Medical School, demonstrating how malaria parasites form mutations that make them stubbornly resistant to drug therapy, may hold the key to a new treatments for a disease that afflicts more than half a billion people worldwide.

The scientists developed disease models using yeast and successfully introduced five mutations that make malaria resistant to the anti-malarial drug, atovaquone. The study, featured as the cover story of the April 29 Journal of Biological Chemistry, paves the way for using these models to test new drugs that could suppress malaria's ability to mutate against current therapy. "This is the first quantitative explanation for malaria's drug resistance," said Dr. Bernard Trumpower, professor of biochemistry at Dartmouth Medical School and head of the study. "In addition to confirming the belief that the resistance was due to these mutations, we have created a practical research tool to design new, improved versions of the drug using these resistant strains."

Malaria, transmitted by Plasmodium falciparum, a parasite carried by mosquitoes, has developed resistance to almost every anti-malarial drug introduced in the past 30 years. Although atovaquone is one of the most recent drugs on the market, there is significant evidence that malaria parasites are quickly developing resistance to that drug as well. According to WHO estimates, 40% of the world's population are currently at risk of the disease and approximately 2 million people, mostly children, are killed by malaria annually worldwide. Today marks Africa Malaria Day, organized to promote awareness of the disease in a country where a child is killed every 30 seconds by malaria.

Investigating ways to counter the mutations and sustain the efficacy of anti-malarial drugs, Trumpower and his colleagues continued their work on previous studies using yeast enzymes to explore atovaquone resistance. It is not possible to grow enough malaria parasites to isola
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Source:Dartmouth Medical School


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