Stanford study finds new way to improve seizure treatment

Researchers at the Stanford University School of Medicine discovered that the drug valproic acid (VPA), which is marketed by Abbott under the brand name Depakote, boosts the amount of the protein neuropeptide Y in the brain by about 50%. What’s more, they found that the drug increased the protein in only two parts of the brain – the thalamus and hippocampus, areas associated respectively with petit mal and temporal lobe epileptic seizures. The neuropeptide Y levels in other parts of the brain were unaffected.

VPA has long been a mainstay in treating epilepsy, although how it suppressed seizures has remained a mystery. It has a minimal sedative effect, but brings with it a host of other unpleasant side effects, including weight gain, hair loss, and liver problems.

Discovering that VPA triggers an increase in neuropeptide Y not only helps explain how VPA works, it also suggests a possible way to stimulate the brain to quell seizures. The key could be to increase the amount of this anti-epileptic compound in the brain.

The precise nature of this response to VPA offers the promise of a new approach in treating seizures.

Unlike VPA, most anti-epileptic medications work by binding to various channels or receptors on neurons throughout the brain, thereby directly slowing the pace of signal transmission and reception. This approach to treating epilepsy is effective because seizures occur when neurons are overstimulated and begin firing too rapidly and in unison, sending pulsing barrages of signals coursing through the brain. Slowing the pace of communication among the neurons prevents them from becoming overstimulated.

However, a seizure often originates in just one part of the brain, so preventing seizures by slowing down the entire brain is like trying to stop cars from speeding on one particular thoroughfare by installing speed bumps on every street in a town.

The researchers said that, if a way could be found to increase neuropeptide Y only in the part of the brain from which a particular type of seizure emanates, it might be possible to develop anti-epileptic medications with few, if any, side effects.

Dr Robert Fisher, professor of neurology and neurological sciences at Stanford and a practicing clinician who treats epileptic patients, said the findings point to a potentially better way of treating the disease. “All of our seizure medications are controlled poisons, all with significant side effects,” he explained. “If we can find out more about the natural mechanisms that produce seizures, then we can hopefully counteract it with a rifle bullet rather than a shotgun that causes all kinds of side effects.”