09:58am Sunday 29 March 2020

Discovery to help stem malaria’s drug defiance

Researchers from ANU have identified the process by which a protein in the malaria parasite counters the anti-malarial effect of chloroquine, shifting the drug away from its site of action inside the parasite’s internal digestive compartment. Their results are published in the journal Science later this week.

Dr Rowena Martin headed up the latest malaria research.
Dr Rowena Martin headed up the latest malaria research.

The discovery is good news for the billions of people at risk from the disease – which causes up to three million deaths each year and imposes massive economic burdens – as it could lead to more effective chloroquine-like drugs or ones that reverse the parasite’s ability to resist drug treatment.

“People forget that we don’t have a vaccine for malaria yet, but we do have anti-malarial drugs that can treat the disease,” says Dr Rowena Martin from the Research School of Biology at ANU. “Since chloroquine was developed in 1934, it’s saved more lives than any other drug in history.

“Up until the 1990s, chloroquine was the most effective anti-malarial drug available. It was cheap, safe, and potent. The drug works by switching off the malaria parasite’s ability to convert the toxic iron in our red blood cells into a harmless crystal. It effectively poisons the parasite by attacking its digestive process.

“But in recent decades there has been a sharp increase in the prevalence of strains of malaria that are resistant to chloroquine. Almost 10 years ago scientists determined that resistant parasites possess a mutant protein, but they didn’t know exactly how this protein allowed the parasite to overcome the effects of chloroquine. Since then, there has been a lot of heated debate about how this protein works, but no conclusive evidence one way or the other.”

Dr Martin and her colleagues were able to identify exactly how the chloroquine-fighting protein worked by isolating it in the relatively inert environment of an unfertilized frog egg, and then introducing chloroquine to see how it behaved.

“Our work provides clear, robust evidence that the mutant protein allows chloroquine to escape from the cell’s digestive area, meaning that the drug no longer does its job. Now that we have a clear model for how this protein works, scientists can concentrate their efforts on developing forms of chloroquine that can beat even the resistant strains of malaria. This may lay the foundation for a renaissance in the development of potent quinoline antimalarial drugs.”

The research team includes Rosa Marchetti, Dr Anna Cowan, Assoc. Professor Susan Howitt, Professor Stefan Bröer and Professor Kiaran Kirk from ANU. Dr Rowena Martin is an NH&MRC Biomedical Fellow who also conducts research at the University of Melbourne.

Filed under: Media Release, ANU College of Medicine Biology and Environment, Health, Science
Contacts: Simon Couper, ANU media office 02 6125 4171, 0416 249 241


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