Duke researchers move towards preventing epilepsy

Raleigh News & ObserverJune 20, 2013 

DURHAM — Duke University scientists have developed a way to prevent epilepsy in mice, a promising step in the quest to find a preventative treatment for the disease in humans.

The researchers used a well-known early warning sign of the neurological disease to focus their treatment, said Dr. James McNamara, Professor of Neuroscience in the Duke School of Medicine.

An estimated 40 percent of young children who have a single prolonged seizure will eventually develop epilepsy later in life, and for more than two decades researchers have tried to figure out why, McNamara said.

“How does a fleeting experience lead to a lifelong change in brain function?” he said.

McNamara’s group focused on the activity of a protein receptor found on the surface of neurons, the building blocks of the nervous system. When these receptors receive a certain protein signal, the neurons increase their excitability and eventually a seizure can happen.

In the research published online Thursday in the journal Neuron, McNamara’s group blocked the receptor’s activity for a short period of time immediately after the initial prolonged seizure. With just two weeks of treatment, there was a dramatic reduction in the development of epilepsy later in life.

The study presented “very convincing evidence that the treatment is truly preventative,” said Dr. Michele Simonato of the University of Ferrara in Italy, an epilepsy expert unaffiliated with the research. The study represents “a very important step forward” in the effort to prevent epilepsy, but “it’s still a very long road” to treatment, Simonato said in an interview.

Epilepsy, marked by recurrent seizures, is a common neurological disorder that affects 1 in 26 children, said Patricia Gibson, executive director of the Epilepsy Foundation of N.C. The causes vary, including tumors, malformation, or trauma in various parts of the brain, which makes preventative treatment difficult.

The seizures studied by the Duke research team, originating in the temporal lobe, are not the violent ones seen in movies, but are more subdued episodes of impaired awareness, short-term memory loss, and semi-purposeful behavior such as lip smacking and thigh rubbing. Approximately one third of people with this type of epilepsy have seizures in spite of current drug treatments.

The Duke researchers used mice that were genetically modified so that a certain chemical could be used to change the activity of the targeted receptors. By using this chemical-genetic approach, the scientists could choreograph the timing and mechanism of mouse brain changes in order to better match the way the disorder actually progresses in humans.

“Carefully aligning the animal model with the human condition is of the utmost importance,” said McNamara.

This emerging approach in medical research is important for many varieties of medical maladies. For example, a mouse that is genetically engineered to develop cancer may not be the best equivalent to an older person who slowly develops a tumor over time and only detects it at a late stage.

The Duke research is important because it addressed the underlying cause of epilepsy, not just the symptoms, said Dr. Jaideep Kapur of the University of Virginia, another epilepsy expert not connected to the research.

“These are very exciting findings,” Kapur said in an interview.

Before human treatments for epilepsy can be developed, the ideal start time and length of treatment following the initial seizure must be determined, McNamara said. And translating the chemical-genetic approach into a deliverable drug is another challenge.

McNamara was hesitant to comment on the timeline of future human treatments, but that is clearly the ultimate goal.

“We want to fix sick people,” he said. “We’re working on trying to find drugs that would be effective.”

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