The Future of Epilepsy Medication
Researchers are making progress on a new “on demand” epilepsy pill which can be taken when people feel a seizure starting. The pill has been developed by a team at University College London, UK, led by Professor Dimitri Kullmann.
They explain that about one percent of people worldwide, or 65 million individuals, have epilepsy. About a quarter are resistant to normal treatments, drugs that suppress the excitability of all brain cells and cause side effects.
But the new pill to suppress seizures may help this group, as it works by genetically modifying brain cells, making them sensitive to a compound which is normally inactive. Professor Kullmann describes the process. “First, we inject a modified virus into the area of the brain where seizures arise,” he says.
“This virus instructs the brain cells to make a protein that is activated by clozapine-N-oxide, or CNO, a compound that can be taken as a pill. The activated protein then suppresses the over-excitable brain cells that trigger seizures, but only in the presence of CNO.”
He adds, “At the moment, severe seizures are treated with drugs that suppress the excitability of all brain cells, and patients therefore experience side effects. Sometimes the dose required to stop seizures is so high that patients need to be sedated and taken to intensive care.
“If we can take our new method into the clinic, which we hope to do within the next decade, we could treat patients who are susceptible to severe seizures with a one-off injection of the modified virus, and then use CNO only when needed.
“CNO would be given as a pill in the event that patients could predict when seizures were likely to occur. For example, many people with treatment-resistant epilepsy experience clusters of seizures, where severe seizures are preceded by smaller ones. Seizure risk is also high when people are ill, sleep deprived, or at certain times of the menstrual cycle, so these would all be good times to take the pill as a preventative measure.
“In urgent situations, the compound could be given as an injection. We could even consider a fully automatic delivery system, where CNO was given by a pump, as is done for insulin in some people with diabetes.”
Full details of the treatment are outlined in the journal Nature Communications. The team has tested the pill on rodents and are planning future trials on human volunteers.
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