Malaria infected child. Pictures: REUTERS/MARY F ADAMS
Malaria infected child. Pictures: REUTERS/MARY F ADAMS

Scientists at the University of Cape Town (UCT) have published details of how the potential antimalaria drug MMV048 works, shedding light on how it targets the deadly malaria-causing parasite.

The information may help other scientists in their quest to find new and better antimalaria drugs. Despite advances in controlling the mosquitoes that transmit malaria, the parasite infected 214-million people worldwide and caused 438,000 deaths in 2015, according to the World Health Organisation.

About 90% of those deaths occurred in Africa.

The quest for new drugs is urgent, as resistance to the existing arsenal of antimalaria drugs is rapidly emerging, even against the most effective artemesinin-based therapies.

"Resistance is only a matter of time," said Kelly Chibale, co-author of a paper published on Wednesday in Science Translational Medicine, describing the mechanism MMV048 uses to kill the malaria parasite. Chibale is director of UCT’s Drug Development and Discovery Centre, which announced five years ago it had identified MMV048 as a potential antimalaria drug.

At the time, scientists said MMV048 had the potential to prevent transmission and cure all strains of the disease, as it blocked all the life stages of the parasite, but it was not clear how it worked.

The paper describes in detail how MMV048 targets a key enzyme in malaria cells called phosphatidylinositol 4-kinase.

"This is the first compound in the malaria field with this mechanism to reach human trials," Chibale said.

MMV048 has already been tested for safety in a small phase-1 trial in Cape Town, and is due to enter a much larger phase-2 safety and efficacy trial in Ethiopia later in 2017.

Ethiopia has been chosen for the phase-2 trial because it has a high malaria burden and there are different strains of the disease in circulation.

After testing a potential drug in animals, researchers use phase-1 trials to determine whether an experimental drug is safe in humans. If the results are good, they conduct larger phase-2 and 3 trials to see if the candidate drug is effective, learn more about its safety and side-effects, and compare it to other treatments. Regulators such as the Medicines Control Council require data from clinical trials to approve new drugs.

MMV048 is one of several drugs in the MMV pipeline, which includes a second antimalaria drug candidate identified by Chibale’s unit called UCT943. UCT943 appeared more potent than MMV048 and was more soluble, which meant it would be easier to formulate, Chibale said.

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