A completely new way of suppressing epileptic seizures in rats is reported in a study to be published in the November issue of Nature Neuroscience. The results of the study suggest that glycolysis inhibitors offer a potential new treatment strategy for epilepsy.
Epilepsy affects 1% of people worldwide. Currently available drugs, however, fail to control seizures in a third of patients. Avtar Roopra, Tom Sutula and colleagues were inspired by the fact that, in some patients, severe epilepsy is improved by a diet that completely avoids all carbohydrates. The 'ketogenic' diet has been known for decades, but no one understood why or how it worked. Glycolysis, the process by which carbohydrates are broken down, is inhibited in patients as a result of the diet. The authors treated epileptic rats with an inhibitor of glycolysis, and report that this dramatically reduced the number and severity of seizures in the animals. Roopra and colleagues suspected that one of the glycolysis end products might increase nerve cell excitability; inhibiting glycolysis would therefore reduce nerve cell excitability and the likelihood of seizures. They found that one product of glycolysis, NADH, increases the expression of certain pro-excitability genes in nerve cells, and inhibiting glycolysis reduced the expression of these genes. Author contact: Avtar Roopra (University of Wisconsin-Madison, Madison, WI, USA) E-mail: roopra@neurology.wisc.edu Tom Sutula (University of Wisconsin-Madison, Madison, WI, USA) E-mail: sutula@neurology.wisc.edu Abstract available online. (C) Nature Neuroscience press release.
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