A new study published in the leading scientific journal Scientific Reports describes how cellular abnormalities caused by defects in a gene called GRIN2A may lead to epilepsy.  Understanding the exact mechanism of how seizures develop at the cellular level could help scientists design better treatments against them in the future.It was already known that mutations in the GRIN2A gene are associated with different types of childhood epilepsies. However the exact effect of the mutations on brain cells was not well understood.In the present study, researchers led by Dr Laura Addis, at Eli Lilly Research Centre in Windlesham, Surrey showed that mutations in the GRIN2A gene lead to the GRIN2A protein being trapped inside nerve cells. The GRIN2A protein is normally found on the cell surface at the junctions between two nerve cells. There, it functions as a “channel” allowing the passage of electrical signals form one nerve cell to the other.The researchers think that in the absence of GRIN2A protein, or if the GRIN2A protein does not function properly, the passage of electrical activity is affected, increasing the risk of epilepsy.Importantly, the team showed that it was possible to restore the activity of the GRIN2A protein using a chemical compound in cells carrying the same mutations in the GRIN2A gene as in people with epilepsy. This is an exciting finding as it suggests that it may also be possible to restore the function of the GRIN2A in patients, offering a potentially treatment against seizures.”This study is important as it shows that mutations in GRIN2A cause the protein produced to malfunction in different ways, leading to epilepsy,” said the first author of the study, Dr Laura Addis in a press release. “By understanding exactly what is going wrong in children with defects in GRIN2A, we can now try to work out what medicines target the pathways in the nerve cells that aren’t working properly”.Professor Deb Pal at the Institute of Psychiatry, Psychology & Neuroscience at King’s College London and a co-author of the study added: “Personalised medicine is the future of epilepsy treatment and will involve prescribing treatments based on the specific effects of a patient’s genetic defect”. He said that scientists need to develop methods to screen different medicines to see if they can restore the function of the defective GRIN2A protein. “As the mutations cause the protein to malfunction in different ways, we will need to work out strategies for the different types of effect,” he explained. “Some medicines will need to be able to get the protein to the cell surface, whereas others will need to make the protein work more, or less effectively, depending on the type of mutation.”Author: Dr Özge Özkaya  What is GRIN2A?  Information from the US National Library of Medicine