Malaria parasites tricked into ingesting drugs

Scientists at The Australian National University (ANU) and the Humboldt University of Berlin have developed a ‘Trojan horse’ method that tricks malaria parasites into ingesting a fatal dose of drugs by exploiting the parasite’s need for cholesterol to survive.

By attaching cholesterol to drugs, the scientists can ‘smuggle’ these drugs into the parasite, where they can exert their killing effect. Their research has been published in the journal EMBO Molecular Medicine.

“Due to its bad reputation, people often forget that cholesterol is a basic building block of life and humans and animals need it to function and survive,” said ANU Professor Alex Maier. “Parasites are particularly desperate for cholesterol, since they have lost the ability to make their own.

“Since parasites can’t produce cholesterol of their own, they steal it from their hosts and stockpile it.”

After a mosquito injects malaria parasites into humans, the parasites eventually enter red blood cells where they hide from the immune system. And although malaria can be cured with drugs, parasites are continually finding new ways to adapt and build resistance to current therapies. The scientists say that their technique, which disguises the drugs under the veil of cholesterol, addresses this longstanding issue.

“Existing drugs used to treat malaria are taken up passively by the parasite, meaning they’re not as effective as they could be,” Maier said.

“By attaching the drugs to cholesterol, the parasite actively latches onto and eats the cholesterol. This allows us to smuggle drugs into optimal killing zones inside the parasite where the drugs can inflict the most damage.

“Using this approach, we can also repurpose existing drugs that have lost their bite and make them effective again. Essentially, we’re giving new life to existing drugs that have since become redundant.

“This research also paves the way for the development of new, more efficient drugs that are also cheaper to manufacture.”

Maier said the method of coupling drugs with cholesterol is 3–25 times more effective at eliminating the parasites compared to drugs that aren’t attached to cholesterol. It could also be used to treat other diseases, including giardia (an intestinal disease responsible for causing diarrhoea) and leishmaniasis — a skin, mouth, nose and throat disease that disproportionally impacts some of the world’s poorest people.

Maier said the research could also unlock new and more effective therapies to treat parasitic diseases in companion animals and livestock. This would prevent billions of dollars in damages and provide a major boost to the agricultural industry, including in Australia.

Image caption: Professor Alex Maier says the new method could lead to more effective and longer-lasting treatments for malaria. Image credit: Jamie Kidston/ANU.