Three newly discovered molecules could help create better epilepsy drugs

An Irish-led team has discovered three molecules that could potentially be used in new drugs to treat epilepsy.

In one of the largest sequencing projects of its kind, researchers have discovered three molecules that could aid the development of drugs for people with epilepsy whose seizures cannot be controlled with current treatments.

In a study published to the Proceedings of the National Academy of Sciences, the researchers identified and measured levels of more than 1bn strands of microRNAs, small molecules that control gene activity in the brain, to investigate if they were changed in epilepsy.

A small set of these microRNAs were found to always be elevated in those with epilepsy, helping the researchers synthesise drug-like molecules to target them. In preclinical testing, three newly forged molecules were found to stop seizures.

Computer simulations demonstrated how the potential treatments influenced molecule networks inside brain cells by changing the inflammatory response, part of the brain’s immune system that is thought to contribute to seizures.

‘Fulfilling urgent and unmet clinical needs’

The study was led by researchers at the Science Foundation Ireland research centre FutureNeuro, and the Royal College of Surgeons in Ireland (RCSI) University of Medicine and Health Sciences. It was the result of seven years of research involving 35 scientists based in eight different European countries, working in neuroscience, genetics, computer science and synthetic chemistry.

“Our approach to drug discovery has led us to new types of molecules that can be targeted to prevent seizures with hopefully fewer side effects,” said Dr Cristina Reschke, FutureNeuro research fellow and honorary lecturer at RCSI, who was a co-lead author of the study.

“Currently, most drugs used to treat epilepsy work by blocking the signals brain cells use to communicate. This results in many of the side effects experienced by people with epilepsy.”

Approximately 40,000 people in Ireland are living with epilepsy and for most of these people, the majority of seizures can be well controlled. While there are more than 20 medicines available to prevent seizures, progress has slowed in recent years, according to the researchers, and new treatments offer little benefit over those that have been around for decades.

Dr Gareth Morris of FutureNeuro, another co-lead on the study, said: “This is an important step closer to fulfilling the urgent and unmet clinical needs for the one-third of people whose seizures are resistant to currently available drugs.”