Two years ago, University of Wisconsin-Madison scientists reported they had suppressed epileptic seizures in rats by giving them a glycolytic-inhibitor, inhibiting the brain's ability to turn sugar into excess energy and blocking the expression of seizure-related genes.
The discovery was greeted with excitement and hope for a new class of drugs for epilepsy, which afflicts more than 50 million people worldwide.
Now, in a presentation at Experimental Biology 2008 in San Diego, Dr. Avtar Roopra describes a next step in this research that may mean a drug already widely used by people with diabetes could also be an effective and safe therapy for epilepsy, especially for that one third of patients who have recurrent seizures despite therapy with the best available antiepileptic drugs.
Dr. Roopra's presentation on April 8 is part of the scientific program of the American Society for Biochemistry and Molecular Biology (ASBMB).
Although the earlier work by Dr. Roopra and his colleagues marked the first time a compound had been used for metabolic regulation of neuronal genes, epilepsy patients had been attempting to achieve the same goal - fewer seizures - for centuries through severe dietary restriction, in some cases with near starvation, more often with a high-fat, high-protein diet completely free of starches and sugars. Half of all drug-resistant people with epilepsy experience seizure control with this kind of severe ketogenic diet (although even a mild lapse can sometimes result in seizures).
The mechanism was completely unknown but the researchers reasoned it had to involve glycolysis, the recognition of sugar and its conversion to energy. And if that were correct, they asked, could they tap into this same biological pathway, bypassing dietary requirements altogether? The answer, published in Nature Neuroscience in October 2006, was 2-Deoxy-D-glucose, a compound that tricked the body into thinking it was sugar so that the cells stopped using the real thing as an energy source.