Major Breakthrough in the Treatment of Malaria By Trinity College Researchers
Posted on: 26 February 2007
Researchers in Trinity College Dublin and Oxford University have discovered a key gene providing a major breakthrough in the treatment of in malaria. The findings by the TCD team of researchers which was led by the College’s Professor of Molecular Immunology and Head of the School of Biochemistry and Immunology, Luke O’Neill along with an Oxford team led by Professor of Human Genetics, Adrian Hill at the University of Oxford have just been published in the world-leading journal, Nature Genetics.
Their research shows how the important immune system protein called Mal plays a major role in determining whether individuals become infected with and ultimately succumb to malaria. They also show that Mal has a protective role against tubercolosis and pneumonia, and possibly many different infections. These insights represent a major advance in our understanding of how the immune system works during infection and indicate possible new therapies to use in the treatment of malaria and other infectious diseases.
Mal was originally discovered in Professor O’Neill’s laboratory in 2001. Commenting on the significance of the discovery, TCD’s Head of the School of Biochemistry and Immunology stated: “We knew we had found an important part of the immune system, but this recent discovery clearly identifies Mal as being important for our immune system’s capacity to fight infections such as malaria.” Mal is in effect an alarm system for the immune system. When the body is infected with the malaria parasite or other germs, a set of sensors called Toll-like receptors (TLRs) lock onto the intruder. TLRs relay the detection via Mal, which wakes up the immune system to mobilise and defend us. The Oxford group discovered that Mal comes in two types in humans. One of the types is suitable for the immune system to work normally, whereas the other type actually results in too strong a stimulation. If you have the overactive type, you are twice as likely to succumb to infection because your immune system goes into over-drive and disease results, in a manner akin to ‘friendly fire’. “Our work provides a striking example of how a key molecule in our immune system can be sacrificed to give some people better resistance to infectious disease,” commented Oxford’s Professor Hill.
Over 6,000 patients with malaria, TB or pneumonia were studied, in the Gambia, Vietnam, Turkey and the UK. Having the overactive Mal doubled the risk of disease, with a four-times greater risk of severe malaria in some populations. The work suggests that drugs that target the Mal pathway might be very useful in the treatment of malaria and TB. “We are very excited by the prospect that our work might be useful in the effort to come up with new strategies to prevent death during these infections,” said Professor O’Neill. Malaria and TB account for over five million deaths per year in the developing world, particularly in children.
The TCD research has been funded by Science Foundation Ireland and the Oxford research has been funded by the Wellcome Trust.