There are no translations available.
Dr Sarah Dunstan - Head of Human Genetics, Oxford University Clinical Research Unit
Variation in the LTA4H gene has been identified to change a tuberculosis patients’ response to treatment. Even though personalized medicine is becoming more widely known in cancer medicine, the idea of it in infectious diseases is much less established. Scientists and clinicians at the Oxford University Clinical Research Unit (OUCRU), the Hospital for Tropical Diseases, Pham Ngoc Thach Hospital for Tuberculosis and Lung Disease in Vietnam, and the University of Washington in the USA published their findings in the international journal Cell this week (link to Tobin et al 2012).
Elegant experiments from the team at the University of Washington identified LTA4H as a hypersusceptibility gene for Mycobacterium infection in the zebrafish model, which was then confirmed in patients from Vietnam with the devastating disease, Tuberculous Meningitis (TBM; link to Tobin et 2010). Further experiments to unravel the mechanism found that the immune response to Mycobacterium infection could be either too inflammatory, not inflammatory enough, or just right, according to LTA4H genotype. Previously, a randomized controlled trial conducted in Viet Nam established that adjunctive dexamethasone benefitted survival in patients with TBM (link to Thwaites et al NEJM) and steroid use became part of the standard treatment for TBM in Viet Nam. These latest findings part-funded by the Wellcome Trust and reported in Cell (link to Tobin et al 2012) support the theory that steroid use in the treatment of TBM may only benefit some patients depending on their LTA4H genotype. Further clinical and genetic studies in TBM patients are on-going at OUCRU to establish this.
For more information see :
Tobin D et al, Cell 148, 434–446, February 3, 2012
Lavani A et al, Cell 148, 389-391, February 3, 2012
Tobin D et al, Cell 140, 717–730, March 5, 2010
Thwaites G et al, N Engl J Med 351, 1741-51, 2004