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

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

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 Prof. Henshall

David Henshall is Associate Professor in Physiology & Medical Physics at the Royal College of Surgeons (RCSI). His laboratory is interested in the cell and molecular mechanisms of brain injury in neurologic disorders such as epilepsy and stroke. Of particularly interest are the role of apoptosis-associated cell death signaling pathways. The group's research approach takes advantage of an array of experimental epilepsy models as well as human brain samples. Major projects are looking at the influence of genes regulating cell death after seziure, the genomic and proteomic responses of the brain to seizures and during the development of epilepsy and also examining experimental therapeutics which might prevent damage to brain after seizure and influence epilepsy itself.

About the Project

Epilepsy is a serious neurologic disorder which affects more than 37,000 people in Ireland. 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:

A short lay summary of the results and outputs of the study can be downloaded in the pdf at the end of the page.

In late 2014, the study results were published in the journal Brain.The paper can be viewed by clicking here.