Scientists identify new epilepsy gene in mice
A gene that causes epilepsy in mice has been identified by an international team of scientists. The human version of the gene is almost identical to the mouse version, and so the findings could eventually lead to the development of new, anti-epileptic drugs. The study is published in the Proceedings of the National Academy of Sciences (PNAS). Epilepsy affects around 1 in 200 people and is characterised by recurrent seizures which are triggered when excess electrical activity in the brain disrupts the ability of the brain cells to communicate with one another normally. The underlying causes of epilepsy are known in less than a third of cases: common causes include brain damage, scarring of the brain tissue, a tumour, or chemical or hormonal imbalances in the brain. The cause of the condition remains unknown in the vast majority of cases, although most of these are presumed to have a genetic origin. Furthermore, a third of patients do not respond to anti-epileptic drugs, and even patients who can be treated with drugs often experience unpleasant side effects, such as weight gain, fatigue and confusion. In this latest study, scientists in Canada, Denmark and the UK investigated a strain of mouse with an inherited form of severe epilepsy. Analyses revealed that the mice had a defective ATP1A3 gene. This gene codes for a protein found in neurons that plays an important role in pumping sodium and potassium ions across the cell membrane. This controls the excitability of the nerve cell by maintaining an electrochemical gradient across the cell membrane. The mice with the defective gene all had seizures displaying the brain activity patterns associated with epileptic fits. In addition, the mice responded well to treatment with the anti-epileptic drug valproic acid, further proving that they were indeed suffering from epilepsy and not another condition that causes similar seizures. Meanwhile, when the epileptic mice were bred with a transgenic mouse that had an extra copy of the healthy version of ATP1A3, the offspring were completely healthy. 'Our study has identified a new way in which epilepsy can be caused and prevented in mice, and therefore it may provide clues to potential causes, therapies and preventive measures in human epilepsy,' commented Dr Steve Clapcote of the Faculty of Biological Sciences at the University of Leeds in the UK. But he warned that there is still a long way to go before this research yields new anti-epileptic therapies. 'However, the human ATP1A3 gene matches the mouse version of the gene by more than 99%, so we've already started to screen DNA samples from epilepsy patients to investigate whether ATP1A3 gene defects are involved the human condition,' he added. 'These results are promising. Not only have Dr Clapcote and his team highlighted a new culprit gene for epilepsy in mice, but they have also shown how normal activity of the affected sodium-potassium pump can be restored,' commented Delphine van der Pauw, Research and Information Executive at Epilepsy Research UK. 'If the findings can be repeated in human studies, new avenues for the prevention and treatment of inherited epilepsy will be opened.'
Countries
Canada, Denmark, United Kingdom