A panel of international researchers has discovered that mutations in a gene called GRIN2D could cause severe epileptic encephalopathy.GRIN2D is part of a gene family containing the information necessary to make proteins called NMDARs. These are ion channels found on the surface of nerve cells, and they play an important role in electrical signalling between them.Mutations in NMDAR proteins are already known to cause childhood epilepsy by over-stimulating nerve signals and causing a toxic build-up of an important neurotransmitter called glutamate. However, until now, it was not known that GRIN2D could harbour disease-causing mutations.The team, led by Dr Marni Falk, from the University of Pennsylvania and The Children’s Hospital of Philadelphia, reported a case of two unrelated children with epileptic encephalopathy in an article published in the American Journal of Human Genetics.The researchers analysed the genes of both children and found a recurrent mutation in the GRIN2D gene in both. Conducting experiments on nerve cells grown in the laboratory, the scientists showed that this mutation causes NMDAR to remain open for too long, resulting in excess electrical signals that kill the neurons.Based on this finding, the scientists gave the children a medicine called memantine, which blocks NMDAR and is already approved to treat people with Alzheimer’s disease. This led to a mild improvements and a modest reduction in their seizures.However, one of the children began to deteriorate over time and had to be placed in an induced coma. Based on the results of previous animal studies, the researchers decided to treat the child with two other NMDAR blockers – magnesium and ketamine. Although neither drug is considered a standard treatment for epilepsy, they produced dramatic improvements, stopping the repeated non-convulsive seizures that the child was experiencing and allowed her to regain some developmental skills.In a press release, Dr Falk said: “Much more work, including randomised clinical trials, remains to be done to learn whether therapies such as these, targeted to a specific gene disorder, can be applied to other patients with similar subtypes of epilepsy.”This is a great example of how basic scientific research can be applied to develop treatments suitable to the unique genetic profile of a patient and reflect the potential of precision medicine.Epileptic encephalopathy is a condition linked to neurodevelopmental disabilities and characterised by frequent seizures that cannot be controlled by common antiepileptic drugs.Author: Dr Özge ÖzkayaClick here for more articles about brain science including genetics.