Current antiepileptic drugs (AEDs) have many side-effects, among others slowing down brain activity, which in turn reduces patients’ ability to react. These side-effects could be eliminated if genes that counteract seizures could be introduced into the brain. Professor Merab Kokaia at Lund University in Sweden has obtained promising results in animal experiments.

Epilepsy is a fairly common condition, affecting around 1 in every 100 people in Sweden. It increases the risk of depression, sudden death, injury and disability. Today’s medication not only has side-effects, it is also not sufficiently effective. A large proportion of epilepsy patients are not helped by the drugs and cannot be treated with brain surgery either.

Research in recent years has shown that the brain tries to counteract seizures. One of the ways it does this is by increasing levels of a protein-like molecule called neuropeptide Y and the expression of certain receptors for it.

Both Merab Kokaia’s research group and others have previously shown that gene therapy can increase levels of neuropeptide Y in the brain. The Lund researchers are now also the first group in the world to introduce genes that increase the expression of certain receptors for neuropeptides in the brain.

“Neuropeptide Y affects many receptors on the cells in the brain. Some of these increase the risk of seizures and thus have the opposite effect to that which we want to achieve. Therefore it is not ideal to only aim for high levels of neuropeptide Y; we should also ensure that the neuropeptide activates the right receptors”, says Merab Kokaia.

He has tested the combined neuropeptide and receptor gene therapy on a rat model of epilepsy and found that the seizures were strongly suppressed. The results have recently been published in the prestigious journal BRAIN.

The genes were introduced into the animals’ brains via harmless viruses. These were injected into the specific parts of the brain that are affected by an epileptic condition.

“If the method works on humans, a single treatment would be sufficient, rather than lifelong medication. Unlike current AEDs, such treatment would also only affect the parts of the brain concerned”, explains Merab Kokaia.

In the USA the Food and Drug Administration (FDA) is now considering an application to test gene therapy for epilepsy on humans. However, this application only concerns introducing genes to increase expression of neuropeptide Y, whereas the Lund group’s findings indicate that genes that increase the expression of the right receptors would be at least as important.

The article is entitled ‘Adeno-associated viral vector-induced overexpression of neuropeptide Y Y2 receptors in the hippocampus suppresses seizures’ and is available at http://brain.oxfordjournals.org/  (enter ‘Kokaia’ in the search box).

Merab Kokaia can be contacted by telephone, +46 46 222 05 47, mobile +46 706 620899, or by email, merab.kokaia@med.lu.se . Photo: Professor Merab Kokaia, Lund University