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MicroRNA Biofluid Profiles as Molecular Diagnostics for Response to the Antiepileptic Drug Leveteracitam

Dr Sinead Heavin, Royal College of Surgeons (Academic Mentor Dr Gianpiero Cavalleri)

€101,790 over two years, of which €30,596 is provided by Epilepsy Ireland. The project is co-funded by the Irish Research Council through its Enterprise Partnership Scheme.

About the project

Levetiracetam (LEV) is a highly effective AED, response to which can be dramatic in that some patients, who previously were refractory to treatment, respond well to LEV. As yet, there is no way of predicting these unexpectedly responsive patients. Biomarkers to identify responders would allow more personalised treatment of the condition.

MicroRNAs (miRNAs) are small molecules made in all cells that control gene expression. Emerging data show miRNA levels are altered in the brain in experimental and human epilepsy. In addition, miRNAs also appear in the blood following injury to the brain including seizures where they are stable and readily detectable, making them ideal potential diagnostic biomarkers.

Biofluid levels of miRNAs differ between patients with drug-responsive versus pharmacoresistant epilepsy. We aim to determine if a patient's miRNA profile can help predict whether they will be a responder to LEV.

This is a retrospective case control study, comparing miRNA profiles across three categories of patients:

  1. Previously refractory patients that are 'late responders' to LEV (n=20)
  2. Refractory patients that also fail LEV (n=20)
  3. Patients seizure free on any drug (n=20). Plasma samples from patients in each group will be analysed to obtain comprehensive miRNA profiles. Comparison across these groups will allow us to identify profiles that are unique to LEV response.

Through this project we will identify microRNA biomarkers for responsiveness to LEV. The identification of a microRNA signature of drug response would represent the first such molecular diagnostic for epilepsy, tailoring treatment to an individual's genetic and molecular make-up and ensuring greatly improved treatment response.