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Genome-wide DNA methylation analysis of hippocampus from patients with pharmacoresistant temporal lobe epilepsy

Principal Investigator:

Professor David Henshall, The Royal College of Surgeons in Ireland

Investment:

€74,312 over 18 months. 50% of the funding for this project has been made available by the Health Research Board (HRB) through the Joint Funding Scheme operated by the HRB and the Medical Research Charities Group, of which Epilepsy Ireland is a member. Epilepsy Ireland will fund the other 50% through fundraising.

About the Project

Research is needed to better understand what causes epilepsy and what effects seizures have on the brain. Previous work has often found abnormal levels of certain genes within the parts of the brain responsible for triggering seizures. If we can understand how gene levels are controlled and how this may be disrupted in patients' brains, this could offer new ways to treat or even prevent epilepsy.

The goal of our proposal is to study a novel mechanism regulating how genes are turned on or off; DNA methylation. This is a chemical change to DNA which effectively switches genes "off". We will perform an analysis of this process using brain tissue donated by patients who underwent surgery for drug-resistant temporal lobe epilepsy. We will look at 385,000 of these DNA changes, thus establishing a DNA methylation "map" of human epilepsy which could contain answers as to why certain proteins/ enzymes are made (or not made).

The results of the proposed research will lead to new information about the way genes are controlled in epilepsy and, we hope, translate into treatments for people at risk of epilepsy development or with difficult to control, long-standing seizures.

Results:

Differential DNA methylation profiles of coding and non-coding genes define hippocampal sclerosis in human temporal lobe epilepsy

Brain, Volume 138, Issue 3, 1 March 2015, Pages 616–631

A short lay summary of the results and outputs of the study can be downloaded in the pdf at the end of the page along with an article from our Epilepsy NEws magazine

 

Downloadable Resources