A new method of fighting malaria, in which the disease is self-stimulating, could provide an effective treatment for the hundreds of millions of people who become infected around the world each year as current antimalarial drugs become less effective.
A study led by the University of Melbourne was published today in Science identified an antimalarial compound, ML901, that inhibits the malarial parasite but does not damage mammalian cells—human or other mammals.
Co-lead author Professor Leann Tilley of the University of Melbourne’s Bio21 Institute said the compound ML901 effectively made the parasite the agent of its own demise, which underlies its potency and selectivity.
“ML901 works through an unusual response hijacking mechanism,” said Professor Tilley.
“Imagine a stealth weapon that allows you to launch a self-destruct attack on your vehicle – by stepping on the brakes and turning off the engine. ML901 finds a particular flaw in the machinery the malaria parasite uses to create the proteins it needs to reproduce itself and stops it from doing so.
“Although there is still much to be done to refine our discoveries, these results are really encouraging for the search for new antimalarial drugs. »
In collaboration with Takeda Pharmaceuticals, Medicines for Malaria Medicine – the leading international organization for the development of antimalarial medicines – and research laboratories on five continents, tests with Takeda-supplied molecules were carried out and the active substance ML901 was identified.
Once inside the parasite, ML901 attached itself to an amino acid and attacked the protein synthesis machinery from within, quickly immobilizing the parasite. The molecular structure of human cells means they are not susceptible to attack by ML901.
In tests using both human blood cultures and a malaria animal model, the team found that ML901 killed malaria parasites resistant to currently used drugs and showed rapid and sustained action, resulting in excellent parasite clearance.
Professor Tilley said the compound has shown activity against all stages of the life cycle, meaning it could be used both to prevent malaria infection and to treat the disease.
“It also demonstrates the potential to prevent infected people from spreading the disease to others, which is critical to halting the spread of malaria.” »
At least 200 million new malaria infections are diagnosed worldwide each year, causing more than 600,000 deaths in Africa and Southeast Asia. Over the past 50 years, ever-increasing resistance to antimalarial drugs has created a looming crisis in which breakthrough drugs are urgently needed.
Professor Tilley said that based on these results, the team is ready to move forward with the development of new drug candidates against malaria.
“We believe this is just the beginning. We now have the potential to find drugs similar to ML901 that target a range of deadly infectious diseases, including multidrug-resistant bacterial infections. The work opens up several new avenues of drug discovery.
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Materials provided by University of Melbourne. Note: Content can be edited for style and length.
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