October 5, 2018

10 Knowledge Gaps in the Discovery and Validation of Blood microRNAs as Biomarkers of Epilepsy – Ways to Close Current Knowledge Gaps

There is a major unmet need for biomarkers of epilepsy. Biofluids such as blood offer a potential source of molecular biomarkers. MicroRNAs fulfil several key requirements for a blood?based molecular biomarker being enriched in the brain, dysregulated in epileptic brain tissue and manipulation of microRNAs can have seizure?suppressive and disease?modifying effects in preclinical models. Biofluid microRNAs also possess qualities favourable for translation, including stability and easy and cheap assay techniques. Here we review findings from both clinical and animal models.

Studies have featured a mix of unbiased profiling and hypothesis?driven efforts. Blood levels of several brain?enriched microRNAs are altered in patients with epilepsy and in patients with drug?resistant compared to drug?responsive seizures, with encouraging receiver operating characteristic (ROC) analyses both in terms of sensitivity and specificity. Both focal and generalized epilepsies are associated with altered blood microRNA profiles and associations with clinical parameters including seizure burden have been reported. Results remain preliminary, however. There is a need for continued discovery and validation efforts that include multi?centre studies and attention to study design, sample collection methodology and quality control. Studies focused on epileptogenesis as well as associations with co?variables such as sex, etiology and timing of sampling remain limited.

Researchers identify 10 knowledge gaps and propose experiments to close these. If adequately addressed, biofluid microRNAs may be an important future source of diagnostic biomarkers that could also support forthcoming trials of anti?epileptogenesis or disease?modifying therapies.

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