Epilepsy Treatments' Failure: Gene Link?
New Insights Into Drug-Resistant Epilepsy
April 9, 2003 -- Epilepsy treatments fail for one in three patients. Now there's a genetic clue to what's going on -- and what might help.
There are several good epilepsy treatments that control epileptic seizures. Yet for many patients, none of them work. It's frustrating to the patients. It's frustrating to their doctors. Researchers are frustrated, too. Why? Different epilepsy drugs work in different ways. If one doesn't work, another should. But that isn't the case.
Now, University of London researcher Asra Siddiqui, MD, and colleagues find that a specific variant gene is linked to drug-resistant epilepsy. The gene is called ABCB1. It makes a protein -- also called ABCB1 -- that carries drugs away from the brain.
"Our results suggest new avenues for early molecular prediction of drug resistance in patients with epilepsy," Siddiqui and colleagues write in the April 9 issue of The New England Journal of Medicine.
Having a particular variant of the ABCB1 gene doubles the risk of drug-resistant epilepsy, the researchers found. The finding doesn't prove that the gene variant causes epilepsy treatments to fail. But it does point a finger at the ABCB1 drug-transport system -- a system that allows drugs to enter cells. Now, Siddiqui and colleagues suggest, it might be possible to design new drugs that bypass this system. It might also be possible to design drugs that disable ABCB1. This might make existing epilepsy treatments work better.
In an editorial, Columbia University neurologists Timothy A. Pedley, MD, and Michio Hirano, MD, note that there are many reasons why epilepsy treatments fail. One might be genetic. It's too soon, they say, to use ABCB1 gene variations as a way to predict whether epilepsy treatments will work. But they note that the study of ABCB1 and similar molecules is an exciting area of epilepsy research.
SOURCE: The New England Journal of Medicine, April 10, 2003.