Gene could determine best treatment for TB patients

Washington - In the future, tuberculosis patients may receive treatments according to what version they have of a single ‘Goldilocks’ gene, researchers say.

This is one of the first examples in infectious disease of where an individual’s genetic profile can determine which drug will work best for them – the idea of personalised medicine that is gradually becoming familiar in cancer medicine.

An international research team from Oxford University, King’s College London, Vietnam and the USA found that people generate an immune response to tuberculosis that is ‘too much’, ‘too little’ or ‘just right’, according to what versions they have of the LTA4H gene.

The findings indicate that patients are likely to benefit from different drug treatments depending on their LTA4H gene profile.

Furthermore, the researchers show that steroids used as part of the standard treatment for the most severe form of tuberculosis, TB meningitis, only benefit some patients.

The researchers found that changes at a single position in the human LTA4H gene were associated with treatment response.

Only those having LTA4H genes that led to too much inflammation benefited from the use of the steroid dexamethasone.

There is some suggestion that the steroid could have an adverse effect for those whose LTA4H genes already lead them to have a reduced inflammatory response, though the result is not statistically significant.

“It’s like a ‘Goldilocks’ gene. 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’,’ said Dr Sarah Dunstan Head of Human Genetics of Oxford University Vietnam.

“You are likely to benefit most from a treatment tailored to your own genes,” he4 added.

Dr Guy Thwaites of King’s College London and who lead the clinical study in Vietnam on a Wellcome Trust Fellowship stated: “This is a fundamental discovery. 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 findings could apply much more widely than just in TB meningitis, or other forms of tuberculosis. Since the inflammation pathways governed by the LTA4H gene are central to many infections, there could be implications for many diseases,” Dr Thwaites added.

The results of the study have been published in the journal Cell.