The role of circulating and exosomal miRNAs as biomarkers of drug-resistant epilepsy

Epilepsy is estimated to affect about 65 million individuals worldwide, with up to 30 percent of drug-resistant patients who do not have remission despite appropriate therapy with antiepileptic drugs (AEDs). Therefore, it is important to distinguish drug-resistant epilepsy early in the course of disease to start a specific therapeutical approach as soon as possible. Recently circulating miRNAs have been proposed as promising biomarkers for different neurodegenerative disorders, including epilepsy. MiRNAs are a class of small non-coding RNA that regulate gene expression at a post-transcriptional level. The regulatory mechanisms controlling translation of mRNA transcripts represents to date a largely unexplored aspect of epilepsy. Several studies have demonstrated that miRNAs are differentially expressed in presence of drug-resistant epilepsy, with a specific expression pattern in brain regions connected to the epileptogenic activity. Moreover miRNAs can be transmitted from one neuron to another across the synaptic cleft carried by exosomes. Because of the ability of exosomes to mediate drug efflux, it could be useful to study how they participate in the pathogenesis of drug-resistant epilepsy. There is a need to establish the relationship between miRNA levels in lesional and non lesional drug-resistant epilepsy in order to use miRNAs as biomarkers of specific pathological condition such as intractable epilepsy. We know that circulating miRNAs are stable in serum and their test in blood is broadly accessible, rapid and noninvasive. Previous studies already found a significant number of miRNAs differentially regulated in the epileptic state when compared to control animals, indicating a tight regulation of miRNAs associated with seizures in epilepsy models. Then our intent is also to understand the role of miRNAs in signaling pathways during corticogenesis, identifying differences in miRNA expression between surgical and serum sample. This correlation would be a great goal for clinical practice, supporting the role of the miRNA as biomarkers in drug-resistant epilepsy associated to structural brain abnormalities. To date few studies have investigated the possible role of miRNAs in the pathogenesis of structural brain abnormalities, the heterogeneity of the abnormal cell population, in fact, is a critical limitation in this field of research. Surely the observation of new specific miRNAs associated with drug-resistant epilepsy and structural brain abnormalities will broaden new horizons both for the clinical and the therapeutical approach of until now intractable epilepsy.