Within a decade, people with drug-resistant epilepsy may be able to take a pill to suppress seizures as required, in a similar way to how we take painkillers to relieve a headache.
Around 50 million people have epilepsy worldwide. Of these, about 70% respond positively to anti-epileptic drugs (AEDs). After 2-5 years of successful treatment, the drugs can be withdrawn in 70% of children and 60% of adults without relapses. People who do not respond to drug treatments may instead have to undergo surgery.
Researchers from University College London (UCL) in the UK believe that the new "on demand" seizure suppressant pill they have developed may offer help to this 30% of epilepsy patients who do not respond successfully to AEDs.
The new treatment - which has only been tested on rodents so far - makes brain cells more sensitive to a compound in the brain that is normally inactive.
Senior author of the research behind the new treatment, Prof. Dimitri Kullmann of the UCL Institute of Neurology, explains how the drug works:
"First, we inject a modified virus into the area of the brain where seizures arise. This virus instructs the brain cells to make a protein that is activated by CNO (clozapine-N-oxide), 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."
Currently, severe seizures are treated with drugs that suppress the excitability of all cells in the brain, which results in side effects. If the dose needed to stop a seizure is very high, patients may need to be sedated and taken to intensive care.
The new treatment suppresses the over-excitable brain cells that trigger seizures.
"If we can take our new method into the clinic," says Prof. Kullmann, "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."
Many people with treatment-resistant epilepsy experience clusters of smaller seizures in advance of a severe seizure. Prof. Kullman envisions patients taking the pill in these situations, when they are able to predict when severe seizures might occur.
Other factors that exacerbate seizure risk in this group include illness, sleep deprivation and certain times of the menstrual cycle, so the pill could also be taken as a preventative measure in these scenarios.
The team also suggests other delivery methods - for instance, an injection may be a more appropriate way to deliver the compound in some cases. An automatic delivery system, where the CNO is delivered using a pump - similar to the way insulin is administered to some people with diabetes - is also feasible.
'Completely reversible' treatment avoids permanent side effects
Prof. Kullmann claims that the "new method is completely reversible," so if patients taking the compound experience any side effects then they would only have to simply stop taking the pill.
Medical News Today queried with Prof. Kullmann whether there could be any potential for adverse reactions to occur in patients as a consequence of the modified virus, however. He responded:
"The modified virus has been disabled so it can't make more viruses and spread. The injection involves a minor surgical procedure to make a small hole in the skull and pass a needle through the lining of the brain, but this is far less invasive than epilepsy surgery, which can involve taking out a few cubic centimetres of brain tissue."
Another advantage of CNO is that the compound has a short half-life of just a few hours and only affects the pre-treated epileptic areas of the brain. This avoids the problem of the whole brain being affected, as in the case of seizure-suppressing drugs, or of permanent alterations being made to the brain as with more invasive treatments.
"Short-acting drugs are occasionally used in epilepsy," Prof. Kullmann told us. "However, because they affect the entire brain they have a limited role, and they are typically reserved for stopping severe seizures in the emergency department. The main limitation of short-acting drugs is that they depress breathing and so patients need to be admitted to the intensive care unit. Because we are only proposing to treat the epilepsy focus, our approach avoids this complication."
Recently, we also reported on the partnership of an implantable device used to treat drug-resistant epilepsy with a modeling system that allows the device to predict where the electrical activity in the brain will begin and disperse.
Written by David McNamee