This is the final report for a fellowship grant awarded in 2012 for £249,860 to Dr Mar Matarin at UCL. Mesial temporal lobe epilepsy with hippocampal sclerosis is the most frequent type of epilepsy in people who do not respond well to medication. This type of epilepsy affects some structures of the brain, particularly the hippocampus which is important for learning and memory. As these patients do not respond well to medication, part of these structures often need to be removed to treat the epilepsy, providing a unique opportunity to study the biology of this disorder in brain tissue from a living individual.The brain is composed of a number of different cell types and regions, some of which are more directly affected in epilepsy. This study has looked at the activity of genes in cells of “healthy” and diseased hippocampus in order to understand how the genes work and sometimes go wrong. Because changes in our DNA can change the activity of our genes, the researchers also investigated the possible relationship between changes in our DNA and changes in genetic activity. The results of this study have provided a better understanding of how seizures initiate and continue, and why drugs do not work for some people with epilepsy. The study has also identified genes that potentially carry a greater risk of epilepsy.The data collected in this study has been made available so that it may be used for future epilepsy research. The team at UCL are also continuing their investigations into genetic risk factors for the cognitive impairment suffered by people with mesial temporal lobe epilepsy with hippocampal sclerosis.Dr Matarin said: “I hope future replication and confirmation of these findings will help to identify populations at risk and improved targeting of therapies.”