Background

Epilepsy is a common brain disease characterised by recurring seizures. While many people can control their seizures with medication, about one in three do not respond to available anti-seizure drugs. This has driven researchers to explore new types of treatments that work in different ways, including therapies that target gene activity in the brain.

One promising group of targets are genes called microRNAs. When active, these genes generate regulatory ribonucleic acids (RNA) that dampen the production of proteins in cells. Previous research showed that blocking one particular microRNA, called microRNA-134, could prevent epilepsy from developing in mice. Levels of microRNA-134 are known to be higher in brain tissue from people with temporal lobe epilepsy, the most common form of drug-resistant epilepsy.

However, from a clinical perspective, preventing epilepsy before it starts has limited usefulness, because neurologists still cannot reliably predict who will go on to develop the condition. To move this approach closer to real-world use, it is important to know whether blocking microRNA-134 can reduce seizures once epilepsy is already established. It is also important to understand how it works to calm the brain.

Research

In this study, we aimed to answer both of these questions. Our experiments showed that inhibiting microRNA-134 in mice with long-standing, drug-resistant epilepsy significantly reduced spontaneous seizures. We also demonstrated, using recordings of electrical activity from individual and groups of neurons, that blocking this microRNA made it harder for epileptic tissue to undergo bursts of firing and to fire together or to synchronize.

Impact

Together, the results help explain how targeting this small RNA can counter the hyperexcitable networks in the brain and encourage the further preclinical development of this novel treatment for epilepsy.