Diet may lead to epilepsy drugs

A fatty diet that helps control epileptic seizures may do so by triggering a chemical change in the brain, a discovery that could lead to new treatments, according to a Harvard University study.
The diet may force a protein to switch the brain’s fuel to fat byproducts called ketones from its preferred energy, glucose, according to a study in genetically manipulated mice in the journal Neuron. Making the brain operate on ketones is known to shut down overexcited neurons that cause seizures.
This so-called ketogenic diet is used by epilepsy patients who aren’t helped by seizure-reducing drugs. The patients are only allowed a saltine cracker’s worth of carbohydrates daily, said Gary Yellen, a study author. That’s hard to do, and new treatments based on the diet’s effects in the body may lead to better control of seizures, he said.
“There are kids who go off this diet because they and their parents can’t manage it,” said Yellen, a professor of neurobiology at Harvard Medical School in Boston. “Having a pharmaceutical to help them would be important.”
Epilepsy is a brain disorder that causes repeated seizures, where neurons fire in a disorganized and sudden way, according to the National Institutes of Health. About 3 million Americans are epileptic, according to the Landover, Maryland-based Epilepsy Foundation, an advocacy group.
Mimicking the Protein
Yellen’s coauthor, Nika Danial, an assistant professor of cell biology at the Dana-Farber Cancer Institute, is working on mimicking the protein. That may lead to a treatment, or help researchers look through chemical libraries for something similar, she said.
The diet is very high in fat, with some protein and almost no carbohydrates, triggering the body to use fat as its source of energy and imitating the effects of starvation on the body. That releases ketones, which can provide energy to the brain in lieu of sugar.
In epileptic mice, the scientists tinkered with a protein called BCL-2-associated agonist of cell death, or BAD, to promote ketones and lower levels of glucose. While their seizures decreased, there was no effect in mice that had been genetically altered to take out the protein, providing evidence for how it worked, according to the study.
The switch is much like changing from diesel to unleaded fuel, causing fewer seizures, Yellen said. Something about the swap prevents neurons from firing too much, though the full extent of the changes isn’t clear. Additionally, a ketogenic diet may be effective in some neurodegenerative disorders, Danial said.
“This could have broader implications for the protective effects of being able to reprogram what the brain burns,” Danial said.
The study was funded by Harvard Catalyst, Citizens United for Research in Epilepsy, and the NIH.