MicroRNAs in the mechanism of ketogenic diet therapies and as biomarkers in paediatric epilepsy

'MicroRNAs in the mechanism of ketogenic diet therapies and as biomarkers in paediatric epilepsy' image

PROJECT TITLE:

MicroRNAs in the mechanism of ketogenic diet therapies and as biomarkers in paediatric epilepsy

PRINCIPAL INVESTIGATOR:

Prof David Henshall
Professor of Molecular Physiology & Neuroscience, Royal College of Surgeons in Ireland

INVESTMENT:

€144,484 over three years. 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:

Prof. Henshall is the Director of the Experimental Epilepsy Research group at RCSI. His team currently comprises 10 researchers whose major research focuses include the role of non-coding RNA (including microRNA) in the development of epilepsy, the modelling and treatment of neonatal seizures, ATP-gated ion channels as targets for seizure control, and molecular biomarkers of epilepsy. Prof Henshall is also Co-Director of The Centre for the Study of Neurological Disorders, also based at RCSI.

ABOUT THE PROJECT:

Prof Henshall explains:

Epilepsy is a disease caused by imbalances in electrical activity in the brain. Anyone can have epilepsy but it is particular common in children. Patients experience seizures which disrupt their lives and can be directly harmful to the developing brain. Although we have a number of drugs to stop seizures, they fail to work in about a third of children. The ketogenic diet (KD) represents an alternative treatment. Clinical and scientific studies show that by altering how much fat and carbohydrates are consumed this switches how the body obtains its energy. For reasons we do not understand this reduces the occurrence of seizures. A key problem is that only half of children placed on the diet show an improvement. Doctors need something to help them know who will respond.

We are interested in a group of molecules found in cells called microRNAs. Their job is to dampen down gene activity by reducing protein levels. Recent work showed that microRNAs are important for controlling the excitability of the brain. We and others have found that blood levels of some microRNA are different in adults with epilepsy. We think this is because the brain makes unique microRNAs and stress or injury such as occurs in epilepsy results in the appearance of these molecules in the blood. We also have animal model evidence that the ketogenic diet directly alters brain levels of certain microRNAs.

The proposed research will investigate whether microRNA levels in blood samples or other body fluids (urine, saliva) can tell us which children with epilepsy will do best on the ketogenic diet. These studies will give doctors a new way to predict which children will do best on the diet and shed new light on how the diet works.