Saturday, July 22, 2006

Targetting Drug Therapy using Genetics

The July 11th online edition of Proceedings of the National Academy of Science, carried an article by Dr Stephen Liggett, on "Genetically targetted theraphy for heart failure". Actually, Dr Liggett had worked retrospectively, analysing the data from the 1999 trial BEST. BEST was a 10,000 patient heart failure placebo controlled trial, comparing the beta-blocker Bucinolol (BMS) to a placebo, in patients with heart failure. The trial was largely negative, where the primary endpoint was not met.

Dr Leggett and team noticed that some secondary endpoints were met and that there seemed to be a racial bias in the results, that blacks did not respond to bucinolol as well as whites. Dr Leggett and team were also fortunate in that the BEST investigators had the foresight to keep DNA samples of the cohort. So Dr Leggett and team analysed the DNA samples and found polymorphism among the patients with heart failure. They found some genetic difference in the responders and non-responders, some amino acid difference in position 389 of the beta receptor. Those with the AA arginine seem to respond better then those with AA glycine at position 389. They have publish their findings and BMS may apply for FDA approval for the use of bucinolol in patients with heart failure, with AA arginine in beta receptor position 389. Whether the FDA will approved this or not, is left to be seen, but it surely is interesting that we are using genetic analysis to help us to target drug therapy.

Can you imagine the situation when we can use the genome project to help us predict drug responses, and also drug side effects so that we can use drugs to those who will respond and who will not get serious side effects. This is the medicine of the future.

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