July 26, 2023

Single Target, Multiple Possibilities: MicroRNA Holds Promise for Epilepsy Treatment 

Article published by News Medical Life Sciences

Featuring the work of former CURE Epilepsy grantee Dr. David Henshall


In a recent study published in the PNAS Journal, a group of researchers investigated the role of micro-ribonucleic acid (miRNA) miR-335-5p as a potential therapeutic target for epilepsy by regulating neuronal excitability through the modulation of voltage-gated sodium channels (VGSCs). 


Epilepsy affects millions of individuals worldwide, and current antiseizure medications (ASMs) target VGSCs. However, some forms of epilepsy, like Dravet syndrome, are treatment-resistant due to loss of VGSC function. To develop better therapies, researchers are exploring miRNAs that regulate gene expression. 


MiRNAs can control VGSC expression, making them attractive therapeutic targets. Triangulating miRNA datasets and studying miRNA alterations caused by effective ASMs could reveal potential therapeutic miRNAs for epilepsy. 


Cannabidiol (CBD), approved for treatment-resistant epilepsy, is an example of an effective ASM with an unknown mechanism of action, arising the need for further investigation. 


The study focused on investigating epilepsy using animal models. Animals were kept in controlled conditions with a 12-hour light-dark cycle, proper temperature, and humidity, with food and water freely available. 


The researchers used two epilepsy models: the PPS model of temporal lobe epilepsy (TLE) in rats and the pentylenetetrazol (PTZ) model in mice. For the perforant path stimulation (PPS) model, electrodes were implanted, and seizures were induced using paired-pulse stimuli. For the PTZ model, mice received a convulsant dose of PTZ to trigger seizures. 


Various treatments were administered to investigate their effects on epilepsy. They modulated miRNA through antisense oligonucleotide “antimir” injections and viral particles expressing specific miRNAs. Additionally, they administered CBD, a compound derived from cannabis, to study its potential effects on epilepsy. 


The researchers analyzed miRNA and mRNA expression in the brain tissues of the animals. They also identified miRNA-target interactions and performed pathway enrichment analyses to understand the molecular mechanisms involved in epilepsy.