Abstracts

Rationale: There is an important and unmet need for biomarkers of epilepsy to identify patients at risk of epilepsy development, progression or remission. Epilepsy biomarkers could also support decisions on when and how to treat and differential diagnosis. Imaging and EEG biomarkers are either time-consuming or expensive. A molecular biomarker in biofluids such as blood would help solve this problem. Although several studies have attempted to identify blood biomarkers of epilepsy, focusing on protein-coding transcripts and protein markers, no sensitive and specific biomarker has yet been proven. MicroRNAs are a class of small non-coding RNA that regulate gene expression at a post-transcriptional level. MicroRNAs are important contributors to brain function and emerging animal and human data suggest microRNAs control signalling pathways that influence brain excitability in epilepsy. MicroRNAs are also detectable in various body fluids and their stability as well as link to disease mechanism makes them potentially ideal molecular biomarkers of epilepsy. Methods: To determine whether there are microRNA biomarkers of human epilepsy we collected blood samples from 32 temporal lobe epilepsy patients at two clinical centres during in-patient video-EEG monitoring, along with blood from 32 age- and gender-matched healthy volunteers. We performed genome-wide microRNA profiling (>700 microRNAs) in each sample using the OpenArray analysis platform run on a 12K Flex QuantStudio PCR. Over 200 microRNAs were consistently called present in control plasma, confirming high specificity of the profiling platform. There were expected high levels of known plasma microRNAs including miR-16, miR-24, miR-150 and miR-484 and low or undetectable levels of brain-expressed microRNAs. Results: A number of significantly differentially expressed microRNAs were identified between control and epilepsy samples including known brain-expressed microRNAs implicated in epilepsy. Conclusions: These results support the existence of a set of microRNAs implicated in disease pathogenesis that may be biomarkers of human epilepsy. Funding: This research was supported by funding from the European Union Seventh Framework Programme (FP7/2007?"2013) under grant agreement no. 602130, by Science Foundation Ireland grant 13/IA/1891 and a fellowship from the Iraqi Ministry of Higher Education and Scientific Research.