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Protein Research Could Lead to New Malaria Drugs

Despite the existence of numerous treatment strategies, malaria still kills 2.7 million people each year. What is more, the parasites that cause the deadly disease are becoming increasingly resistant to drugs currently available, making the development of new medications all the more urgent. To that end, a report published today in the journal Science may help. Scientists have identified a key difference in how humans and the malaria-causing parasite Plasmodium regulate a single enzyme. The findings could aid future efforts to design drugs.

Plasmodium is sensitive to drugs that target the enzyme dihydrogolate reductase (DHFR), which humans also produce. Previous research had suggested that the reason drugs could kill the parasite yet leave the host unaffected was because the drugs had a higher affinity for parasite DHFR. Yet some drugs that did not exhibit such selectivity were still toxic only to Plasmodium. With the new work, Pradipshinh K. Rathod and Kai Zhang of the University of Washington explain this discrepancy. They report that the parasite cannot rapidly replenish the enzyme once a drug binds to it because the messenger RNA necessary to produce DHFR is also bound to the enzyme itself. A human cell, in contrast, can rapidly generate surplus quantities of the protein if the drug accidentally attacks it because the messenger RNA is released when the drug binds to DHFR in humans.

The researchers hope the new findings, coupled with the ongoing sequencing of the malaria genome, will lead to more selective drug design to combat the disease. Says Rathod: "You can have all the maps, you can have all the guns, you can have all the firepower, but if you don't know where the important targets are, it's a waste." In a commentary published in the same issue of the journal, Daniel E. Goldberg of the Howard Hughes Medical Institute at Washington University concludes that "with a little planning we should be able to exploit our mammalian sophistication to develop potent antiparasitic drugs."

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