In a discovery that could lead to new treatments for epilepsy, a study led by RCSI University of Medicine and Health Sciences and FutureNeuro has identified a previously unknown ‘master controller’ of electrical signals in brain cells.

The study showed that the molecule could be a useful target for future medicines to help control seizures in epilepsy, which is one of the most common chronic brain diseases, affecting around 65 million people worldwide. Around one in three people with epilepsy have uncontrolled seizures despite being treated with currently available anti-seizure medication.

The study, which was published in the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS), took a broader look at what naturally controls how our brain cells communicate. 

All of our brains need electrical signals to function. These signals begin with the entry of charged sodium ions into neurons through dedicated channels, which act like gates or doorways on the surface of the cells. In people with epilepsy these channels become over-active, leading to higher-frequency signals that generate seizures. 

Calming effect

The ‘master controller’ molecule discovered by the team at RCSI and FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Disease, is called microRNA-335, a type of ribonucleic acid (RNA) that occurs naturally in our brain cells. By sticking to the messages that instruct how to assemble the channels, microRNA-335 lowers the amounts of sodium channels in brain cells. 

In a series of experiments on human-derived cells growing in the lab, the study found that reducing the amount of microRNA-335 in neurons increased the amount of sodium ions that moved into the cells and caused the brain cells to become more excitable. This finding underscores the calming actions of microRNA-335.

The researchers also carried out early, pre-clinical tests in the lab using gene therapy that could deliver microRNA-335 specifically to neurons, and saw that it resulted in an encouraging reduction in seizures.  

Finding this master-controller of sodium channels opens up opportunities to develop new treatments for controlling seizures in epilepsy, according to researcher Dr Mona Heiland from FutureNeuro and RCSI Department of Physiology and Medical Physics.

“Overall, we think that microRNA-335 is acting as a regulator of brain excitability, and could be a potential new target for the treatment of drug-resistant epilepsies,” she said. 

Seizure control

Professor David Henshall, Director of FutureNeuro and Professor of Molecular Physiology and Neuroscience at RCSI commented: “The discovery of this new potential treatment target opens up the possibility of long-lasting and improved seizure control for patients in the future.”

The highly collaborative international project involved many partners, including the Interdisciplinary Nanoscience Centre at Aarhus University and Omiics, both in Denmark; the Epilepsy Center Frankfurt Rhine-Main at University Hospital Frankfurt in Germany; and the Department of Neuroscience, Physiology and Pharmacology at University College London.

The research was funded by Science Foundation Ireland, Framework Programme 7 and the Wellcome Trust.