Twins may hold secrect for treating Tuberculosis
Tuberculosis is the world's most deadly single infectious disease: the causative bacterium Mycobacterium tuberculosis infects one in three of the world's population, afflicting 200 million with serious symptoms during their lives, and killing almost two million each year.
Antibiotics that can tackle it are too expensive for some developing countries to provide for all those with the disease and the current vaccine is not always effective. But a project by Dr Melanie Newport, which looks at twins in the Gambia, suggests that a genetic approach to treatment could be an important step forward.
Mycobacterium tuberculosis infects the lungs and can go on to attack many other parts of the body, such as the bones and central nervous system. This happens if the patient’s immune system is weakened and the body is not making the molecules and chemicals it usually produces to fight bacteria.
The usual reasons that immune systems do not function properly is that people have another illness such as HIV/AIDS, or are malnourished or elderly. But these factors cannot account completely for the fact that one in 10 of those infected go on to develop serious Tuberculosis (TB) disease symptoms after initial infection but the rest do not.
Dr Newport from Brighton and Sussex Medical School, is carrying out research which suggests that some people develop TB symptoms because the genes that would normally organise a good immune response to the disease are not functioning normally – for example they could be switched off by Mycobacterium tuberculosis. If her research team can discover which genes are switched off, they may be able to find a way to turn them back on and so restore patients’ immune systems to full working order.
In order to test the idea, the research team is looking at young babies who are given a vaccine which boosts their immune system so that it can tackle TB infection. Some babies develop a weaker immune response than others to the vaccine and this is partly because some of their genes are not functioning normally. By analysing the genetic differences between the babies, the researchers can tell which genes are involved in producing a good or bad immune response. It is easiest to do this with twin babies by comparing genetically identical twins with non-identical twins to find difference in the genes that control the immune system. Since the Gambia has high rates of twins who all receive the TB vaccine at birth because of the high rates of the disease, the research is being carried out there.
Once the researchers identify which genes are switched off, they can work on producing a treatment which can be given to TB patients in order to switch the genes back on, boosting the immune response and curing the disease. They have now narrowed their search to about 600 genes and are fine-mapping this further.
They believe that the genes, once switched on, could increase the production of a chemical called interferon-gamma, which is important for immune response.
Dr Newport's work is funded by the Wellcome Trust and the British Lung Foundation.
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