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New epilepsy treatment offers ‘on demand’ seizure suppression

28 May 2014

A new treatment for drug-resistant epilepsy with the potential to suppress seizures ‘on demand’, has been developed by researchers in the Department of Clinical and Experimental Epilepsy, UCL Institute of Neurology, led by Professor Dimitri Kullmann.

Epilepsy seizure suppression schematic

The treatment, described in Nature Communications, combines genetic and chemical approaches to suppress seizures without disrupting normal brain function. The technique was demonstrated in rodents in experiments carried out at the UCL Institute of Neurology by first author Dennis Kätzel, but in future we could see people controlling seizures on-demand with a simple pill.

“First, we inject a modified virus into the area of the brain where seizures arise,” explains Professor Kullmann. “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.

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.

Professor Dimitri Kullmann

As CNO has a half-life of about a few hours and only affects the pre-treated epileptic parts of the brain, the new method avoids the need to permanently alter the brain or treat the whole brain with seizure-suppressing drugs. It builds on similar work by Professor Kullmann and his colleagues Matthew Walker, Stephanie Schorge and Robert Wykes, using gene therapy to ‘calm down’ brain cells, or using light pulses to activate seizure-suppressing receptors in the brain. The new technique works in a similar way but is reversible and avoids the need for invasive devices to deliver light to the brain.

This makes it more attractive than alternative forms of targeted therapy such as surgery to remove the brain region where seizures arise, or gene therapy that permanently alters the excitability of brain cells. Although there is currently no evidence that permanently suppressing excitability in a small area affects brain function, we cannot be sure that it would have no impact long-term. Our new method is completely reversible, so if there were any side-effects then people could simply stop taking the CNO pill.

Professor Dimitri Kullmann

Further information

Kätzel, Nicholson, Schorge, Walker, Kullmann, Chemical-genetic attenuation of focal neocortical seizures. Nature Communications. Available online 27th May 2014. DOI: 10.1038/NCOMMS4847

UCL press release

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