Potent Anti-Seizure Effects of D-leucine

A team of scientists from Johns Hopkins University (Baltimore, MD) may have identified an amino acid with the potential to inhibit seizures. The research was conducted in an attempt to better understand the amino acid D-leucine, which, though present in a number of foods and bacteria, has remained a mystery with regard to its biological function. Because other amino acids found in high-fat ketogenic diets have been shown to prevent seizures through the production of metabolic byproducts, the researchers evaluated the impact of D-leucine on prolonged seizures in an animal model.

The findings, published in Neurobiology of Disease, revealed that D-leucine was effective for reducing the mice’s susceptibility to seizures and for stopping convulsions already in progress.
Next, the scientists compared the effectiveness of D-leucine with that of the popular epileptic drug diazepam. They found that the amino acid was at least as successful at terminating seizures as the drug. Mice treated with D-leucine also resumed normal activities about 15 minutes earlier than those treated with diazepam and experienced none of the sedative effects associated with the drug. Additionally, the mice were responsive to D-leucine treatment even when exposed to only very small doses.

Finally, the team tested whether D-leucine binds to neuronal receptors involved in synaptic transmission and known to play a role in seizure activity (bit.ly/1CnqAd9). The team found that the amino acid did not interact with the candidate receptors, suggesting that D-leucine has a unique mechanism from any other therapies for treating epileptic seizures, opening up the possibility that new approaches to treatment may succeed where others have thus far failed.

J. Marie Hardwick, the David Bodian Professor in Microbiology and Immunology at Johns Hopkins Bloomberg School of Public Health (Baltimore, MD), and the senior investigator, says that her team’s findings could mean that “D-leucine affects neurons differently from other known therapies,” and that the discovery “gives us hope of new approaches to epilepsy on the horizon.” — Sean McGuire