Epilepsy gene discovered; could lead to new treatments

Dr. John Roder, Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital, has developed a method to prevent epilepsy caused by a gene defect in mice – an achievement which may herald new therapies for people suffering from the condition. The study, published in the August 3, 2009, US Journal Proceedings of the National Academy of Sciences (PNAS), offers for the first time evidence that a faulty version of a gene known as Atp1a3 is responsible for causing epileptic seizures in mice.

Epilepsy affects almost one per cent of the world’s population, and yet the causes of this disorder are largely unknown. Current treatments are ineffective in approximately 30 per cent of epilepsy patients.

“Our results are very promising, but there’s a long way to go before this research could yield new antiepileptic therapies. However, the human ATP1A3 gene matches the mouse version of the gene by more than 99 per cent, so we’ve already started to screen DNA samples from epilepsy patients to investigate whether ATP1A3 gene defects are involved the human condition,” says Dr. Roder.

To prove the gene’s role, the team created a special strain of mouse, called Myshkin, which has an inherited form of severe epilepsy. The researchers found that these mice have a defective Atp1a3 gene, which led to them all having spontaneous seizures displaying the characteristic brain activity of epilepsy. To confirm that the seizures were epileptic, the team showed that mice treated with an antiepileptic drug, valproic acid, had fewer, less severe seizures.

When the epileptic Myshkin strain was bred with a transgenic mouse strain that has an extra copy of the normal Atp1a3 gene, the additional normal gene counteracted the faulty gene - resulting in offspring which were completely free from epilepsy.

The research was supported by funding from Canadian Institutes of Health Research.