Scientists have identified a new way to stop malaria parasites from multiplying, an important step in developing new treatments for the disease, which killed an estimated 1.2 million people in 2010.
The activity of an enzyme called NMT is essential for the survival and viability of the most common malaria parasite. Researchers are working to design molecules that inhibit NMT’s function, and hope to start clinical trials of potential treatments within four years.
Although a variety of antimalarial drugs are available, some strains of the parasite are resistant to treatment. These strains are becoming more common, with treatment failures reported across multiple frontline drugs.
If acute illness is cured, the parasite can remain dormant in the blood and return to cause illness later. Malaria vaccines have been researched intensively, but none have been introduced into clinical practice.
Published in Nature Chemistry, the new study shows that NMT is involved in a wide range of essential processes in the parasite cell, including the production of proteins that enable malaria to be transmitted between humans and mosquitoes, and proteins that enable malaria to cause long-term infection.
Researchers have tested a handful of molecules that block the activity of NMT in the parasite living inside human red blood cells, but further refinement will be needed before a treatment is ready to be tested in humans.
For the new study, researchers carried out X-ray analysis of crystals of NMT to establish the mechanisms by which these molecules inhibit the action of the enzyme.
How malaria parasites function
“While the research was targeted strategically towards drug discovery, it has given fundamental insights into how malaria parasites function,” says Tony Wilkinson, of the Structural Biology Laboratory at the University of York.
“Here, we’ve shown not only why NMT is essential for a wide range of important processes in the parasite, but also that we can design molecules that stop it from working during infection,” says Ed Tate, from the department of chemistry at Imperial College London, who led the project.
“It has so many functions that we think blocking it could be effective at preventing long-term disease and transmission, in addition to treating acute malaria. We expect it to work not just on Plasmodium falciparum, the most common malaria parasite, but the other species as well.
“We need to do some more work in the lab to find the best candidate molecule to take into clinical trials, but hopefully we’ll be ready to do that within a few years.”
The discovery is the culmination of a five-year project by a consortium of researchers from the University of Nottingham, the University of York, Imperial College London, the National Institute for Medical Research, and Pfizer. The Medical Research Council, the Engineering and Physical Sciences Research Council, and the Biotechnology and Biological Sciences Research Council funded the work.
Source: University of York