DrGary Brennan

Our research is focused on understanding the molecular mechanisms which drive epilepsy development following epilepsy-inciting events. Our research is designed to answer three critical difficulties faced by clinicians and researchers in epilepsy.

Arm 1; Firstly we do not fully understand the mechanisms by which an epilepsy-inciting event causes epilepsy. Towards this end we are studying the immediate and persistent epigenetic and epitranscriptomic changes which take place following epilepsy-causing brain insults which eventually reprogram cells to behave differently, culminating in seizures, behavioral changes and cognitive impairment.

Arm 2; Current anti-epileptic drugs are effective at suppressing seizures in about 66% of epilepsy patients. That means about one third of patients are failed by conventional anti-epileptic drugs. Current treatments do not target the molecular basis of the disease. We therefore do not have mechanism based drugs which treat the underlying causes of the disease or have the potential to reverse already established epilepsy. This arm of our research program employs small molecule inhibitors and/or RNA-based antisense or mimic approaches, based on our findings from arm 1, to try to prevent epileptogenesis following an epilepsy-inciting event.

Arm 3; Presently it is not possible to predict with any degree of certainty patients likely to develop epilepsy following a potential epilepsy-causing disease. We are thus attempting to define molecular signatures in peripheral biofluids such as blood plasma which may predict a likelihood of developing epilepsy. This would allow immediate treatment and in future prevention-based therapies to block epileptogenesis.

Current research is funded by Science Foundation Ireland, Health Research Board, European Union Actions and industry investment.