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Gene variations explain drug dose required to control seizures

Determining which variants of particular genes patients with epilepsy carry might enable doctors to better predict the dose of drugs necessary to control their seizures, suggest basic findings by researchers at the Duke University Institute for Genome Sciences & Policy (IGSP) and the University College London. Patients often undergo a lengthy process of trial and error to find the dose of anti-epilepsy drugs appropriate for them.

The researchers found that variants of two genes were more likely to be found in patients who required higher dosages of anti-epileptic drugs.

The findings suggest that, by incorporating genetic tests into the prescription process, physicians might improve outcomes for patients with epilepsy, said the researchers. A similar approach might also prove useful for other conditions, such as Parkinson's disease and cancer, in which patients' drug dosage requirements vary substantially, they added.

Rigorous clinical study is required before any such method could be put into practice, the researchers emphasized.

In the March 28, 2005, early edition of Proceedings of the National Academy of Sciences, the investigators report the first clear evidence linking variation in genes involved in the action or metabolism of the anti-epileptic drugs, carbamazepine and phenytoin, to the drugs' clinical use. The study is the first to emerge from a partnership, aimed at tailoring the treatment of epilepsy to patients' genetic makeup, between the Department of Clinical and Experimental Epilepsy at the University College London and the Duke Center for Population Genomics and Pharmacogenetics, a center of the IGSP.

If the genes' predictive value is verified in clinical trials, such a "pharmacogenetic" approach might make it possible to safely reduce the time required for patients with epilepsy and their physicians to reach an effective dose of the medications that control seizures, said David Goldstein, Ph.D., director of
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Source:Duke University Medical Center


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