New malaria drug could help combat resistance

Drug resistance has reached crisis levels everywhere, but its impact on malaria treatment has been particularly devastating. The mosquito-borne parasite Plasmodium falciparum, which causes the deadliest form of the disease, has developed resistance to every drug currently available. Millions of people continue to die from malaria every year.

Now, Dr Aaron Nilsen and colleagues have discovered a new drug called ELQ-300 that can target multiple stages of the malaria parasite’s life cycle, including the liver stage, and could dramatically boost the prevention, treatment and transmission of disease. Their research appears in the journal Science Translational Medicine.

A chemical model of ELQ-300. [Image courtesy of Michael Riscoe]

Dr Michael Riscoe, a co-author of the study, explained in an AAAS podcast that the drug works by selectively targeting the Plasmodium parasite’s mitochondrion. The main function of mitochondria in malaria parasites is to produce building blocks needed to make DNA, called pyrimidines. ELQ-300 is able to completely block this process.

“Studies show that the drug acts very quickly to shut down this process; in fact, only about 10 minutes,” said Dr Riscoe. “But it takes several days for the parasites to die, since they can no longer reproduce.”

The researchers also found that ELQ-300 is 30 times more effective at treating malaria in mice compared with atovaquone, a drug in clinical use today. At doses 10 times lower than typically used, the drug completely protected mice from infection by mosquito transmission.

Dr Riscoe stated that although malaria parasites have “an enormous capacity to adapt and survive in humans”, it appears to be very difficult to select for ELQ-300 resistant parasites by classical methods.

“These findings suggest that if the drug is developed for human use, then it could enjoy a long, useful clinical life before resistance emerges in the field,” he added.

However, Dr Riscoe noted, “The World Health Organization advises strongly for new drugs to be released in combination with other drugs to prevent or delay the onset of resistance. So of course, there is the need to match ELQ-300 with another drug for combination chemotherapy.”

Other barriers also include conducting safety tests and finding a clinical formulation for the drug that can be used in humans. Dr Riscoe has suggested that the drug would be milled into nanoparticles to enhance absorption in the intestines and to deliver it to the bloodstream.