‘Goldilocks’ gene dictates TB response
9 Mar 2012 by Evoluted New Media
A ‘Goldilocks’ gene that dictates whether your response to tuberculosis is ‘too much, ‘too little’ or ‘just right’ may determine the best treatment for the disease.
An international team of researchers – including teams from the University of Oxford and King’s College London – found that people generate an immune response to tuberculosis (TB) dependent on what version of the LTA4H gene they have. Patients are therefore likely to benefit from different drug treatments depending on their LTA4H gene profile.
“It’s like a ‘Goldilocks’ genes,” said Dr Sarah Dunstan, head of Human Genetics at Oxford University Vietnam where much of the research was conducted.
“Depending on what versions of the LTA4H gene you have inherited, you could see an inflammatory response to tuberculosis that is ‘too much’, ‘too little’ or ‘just right’. You are likely to benefit most from a treatment tailored to your own genes.”
Most TB affects the lungs, but around 40% of cases involve disease elsewhere – in 1-2% of cases, TB affects the brain, TB meningitis. Standard treatment for TB meningitis involves a range of antibiotics to try and kill the bacteria, and the steroid dexamethasone to dampen inflammation.
However the research – which combined work in zebrafish to identify genes and biological pathways involved in the immune response to TB, with clinical research work – showed steroid use only benefitted some patients.
The scientists identified a gene in zebrafish associated with susceptibility to TB, which controlled the balance of inflammatory response. Variations in the DNA code in this gene could alter different biological pathways, leading to variations in inflammation. Both too much and too little inflammation is problematic and allows TB to thrive and multiply.
By blocking the appropriate biological pathways with drugs, researchers – who published the research in Cell – found they could restore just the right level of inflammatory response.
“This is a fundamental discovery,” said Dr Guy Thwaites from King’s. “It is now possible to think about the use of simple but rapid genetic tests to determine how people will respond to tuberculosis infection and whether they would benefit from steroids.”
“The idea that a patient’s genes can determine what treatment they will benefit from is pretty novel outside of cancer,” said Professor Jeremy Farrah. “Nothing like this has been seen before in infectious disease. Now we need to see if we can use this to help patients with this devastating disease.”
