Children with epilepsy, who aren’t helped by anti-seizure medication, are treated with a ketogenic diet that is high in fat and low in carbohydrates. The ketogenic diet mimics effects of starvation.
Neurologists were never quite sure why the diet works well with epilepsy. In a new study, scientists say they may have found the answer. Researchers at Dana-Farber Cancer Institute and Harvard Medical School said seizures could be linked to a protein that changes metabolism in the brain. The protein, called BCL-2-associated Agonist of Cell Death, or BAD, also regulates metabolism of glucose, which is why epileptic patients respond to the ketogenic diet.
“The connection between metabolism and epilepsy has been such a puzzle,” said Yellen, who was introduced to the ketogenic diet through his wife, Elizabeth Thiele, HMS professor of neurology, who directs the Pediatric Epilepsy Program at MassGeneral Hospital for Children, but was not directly involved in the study. “I’ve met a lot of kids whose lives are completely changed by this diet. It’s amazingly effective, and it works for many kids for whom drugs don’t work.”
“We knew we needed to come at this link between metabolism and epilepsy from a new angle,” said Danial, who had previously discovered a surprising double duty for a protein known for its role in apoptosis: The protein, BCL-2-associated Agonist of Cell Death, or BAD, also regulated glucose metabolism.
Giménez-Cassina discovered that certain modifications in BAD switched metabolism in brain cells from glucose to ketone bodies. “It was then that we realized we had come upon a metabolic switch to do what the ketogenic diet does to the brain without any actual dietary therapy,” said Gimenez-Cassina in a press release, who went on to show that these same BAD modifications protect against seizures in experimental models of epilepsy.
The research will be published in the May 24th, 2012 issue of the journal Neuron, and could help lead to the development of new treatments for epilepsy.
“Diet sounds like this wholesome way to treat seizures, but it’s very hard. I mean, diets in general are hard, and this diet is really hard,” said Yellen. “So finding a pharmacological substitute for this would make lots of people really happy.”
Epilepsy is a brain disorder in which a person has repeated seizures, or convulsions, over time. The seizures represent episodes of disturbed brain activity and cause changes in attention and behavior, according to the National Institutes of Health. The condition affects about 3 million Americans and 50 million people worldwide, according to the Epilepsy Foundation. About two in 100 people will experience a seizure at some point in their lives, according to the Mayo Clinic.