Newly Discovered Compound Causes Malaria to Self-Destruct

Researchers in Australia have identified an anti-malarial compounds that turns the deadly parasite against itself—findings that could offer an effective treatment for the hundreds of millions of people infected globally each year. New strategies to control the disease are particularly needed as the efficacy of current antimalarial drugs wanes.

Professor Leann Tilley from the Bio21 Institute at the University of Melbourne, said the ML901 compound effectively makes the parasite the agent of its own demise, underpinning it potency and selectivity. “ML901 works by an unusual reaction-hijacking mechanism,” Tilley says.  “Imagine a stealth weapon that can be used to launch a self-destruct attack on your vehicle—slamming on the brakes and cutting the engine. ML901 finds a particular chink in the machinery that the malaria parasite uses to generate the proteins needed to reproduce itself and stops it doing so.”

In the collaboration with Takeda Pharmaceuticals, Medicines for Malaria Medicine, and research labs across five continents, tests were conducted using molecules provided by Takeda, during which the ML901 compound was identified.

Once ML901 entered the parasite, it attached itself to an amino acid and attacked the protein synthesis machinery from the inside, rapidly grinding the parasite to a halt. The molecular structure of human cells means they are not susceptible to attack by ML901.

In tests using both human blood cultures and an animal model of malaria, the team found ML901 killed malaria parasites that had resistance to currently used drugs and showed rapid and prolonged action resulting in excellent parasite killing.

Professor Tilley said the compound showed it was active against all stages of the lifecycle, meaning it could be used to prevent malaria infections as well as to treat the disease. “It also shows potential for preventing infected people from transmitting the disease to others, which is critical to stop the spread of malaria.”

Every year, at least 200 million new malaria infections are diagnosed worldwide, causing more than 600,000 deaths in Africa and Southeast Asia. Over the past 50 years, ever increasing levels of resistance to antimalarials has led to an impending crisis, with breakthrough drugs desperately needed.

Professor Tilley said based on these findings, which were published recently in the journal Science, the team is ready to pursue the development of new antimalarial drug candidates. “While there is much work to be done to fine tune what we’ve discovered, these results are really encouraging in the search for new antimalarials,” Tilley says.