Scientists have taken an important step towards new malaria treatments by identifying a way to stop malaria parasites from multiplying.
In a study published in Nature Chemistry, they show that blocking the activity of an enzyme called NMT in the most common malaria parasite prevents mice from showing symptoms and extends their lifespan. The team are working to design molecules that target NMT more potently, and hope to start clinical trials of potential treatments within four years.
A recent study estimated that 1.2 million people died from malaria in 2010. 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.
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.
The researchers have tested a handful of molecules that block the activity of NMT in the parasite living inside human red blood cells, and in mice, but further refinement will be needed before a treatment is ready to be tested in humans.
Dr Ed Tate, from the Department of Chemistry at Imperial College London, who led the project, said: "The drug situation for malaria is becoming very serious. Resistance is emerging fast and it's going to be a huge problem in the future.
"Finding an enzyme that can be targeted effectively in malaria can be a big challenge. 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. 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 Imperial College London, the MRC National Institute for Medical Research, the University of Nottingham, the University of York, and Pfizer, funded by the Medical Research Council, the Engineering and Physical Sciences Research Council, and the Biotechnology and Biological Sciences Research Council.
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Notes to editors
1. M.H. Wright et al. 'Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach.' Nature Chemistry, 2013.
After the embargo the paper will be available at: http://dx.doi.org/10.1038/nchem.1830
2. About Imperial College London
Consistently rated amongst the world's best universities, Imperial College London is a science-based institution with a reputation for excellence in teaching and research that attracts 14,000 students and 6,000 staff of the highest international quality. Innovative research at the College explores the interface between science, medicine, engineering and business, delivering practical solutions that improve quality of life and the environment - underpinned by a dynamic enterprise culture.
Since its foundation in 1907, Imperial's contributions to society have included the discovery of penicillin, the development of holography and the foundations of fibre optics. This commitment to the application of research for the benefit of all continues today, with current focuses including interdisciplinary collaborations to improve global health, tackle climate change, develop sustainable sources of energy and address security challenges.
In 2007, Imperial College London and Imperial College Healthcare NHS Trust formed the UK's first Academic Health Science Centre. This unique partnership aims to improve the quality of life of patients and populations by taking new discoveries and translating them into new therapies as quickly as possible.
3. About the University of York
The University of York was founded in 1963 with 200 students. It now has 15,000 students and more than 30 academic departments and research centres.
It is a member of the Russell Group and features regularly in the ranks of the UK's foremost universities. In 2012 two international league tables of the most successful young universities ranked York as No 1 in the UK and No 6 in the world.
It was named Times Higher Education University of the Year in 2010 for its drive to combine academic excellence with social inclusion, and its record in scientific discovery and investment in the arts and humanities. The University has won five Queen's Anniversary Prizes for the quality of its research.
The University of York places equal emphasis on research and teaching. Students in every academic department - both undergraduate and postgraduate - are taught and advised by leaders in their field.
The University has a collegiate system in which most staff and all students are members of one of eight colleges, with a ninth under construction.
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