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Irish-led Global Study Discovers Three Potential New Targets for Stopping Uncontrolled Epileptic Seizures

Findings could lead to drug discoveries for seizures which cannot be controlled with current treatments

An Irish-led international study has uncovered three molecules that have the potential to be developed into new drugs to treat epilepsy.

The findings are an important step towards discovering new drugs for people with epilepsy whose seizures cannot be controlled with current treatments, according to a paper published in the current (May 2020) edition of the journal Proceedings of the National Academy of Sciences (PNAS).

The study was led by researchers at FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases and Royal College of Surgeons in Ireland (RSCI) University of Medicine and Health Sciences.

It was the result of seven years of research, involving contributions from 35 scientists, based in eight different European countries, across the fields of neuroscience, genetics, computer science and synthetic chemistry. In one of the largest sequencing projects of its kind, researchers identified and measured levels of over a billion strands of microRNAs, small molecules that control gene activity in the brain, to investigate if they were changed in epilepsy.

They discovered a small set of microRNAs which were always elevated in epilepsy and designed drug-like molecules, synthesised by chemists from the group, to target these.

Three of the synthetic molecules were found to stop seizures in preclinical tests.

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 which is thought to contribute to seizures.

“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, and Co-Lead Author.

Epilepsy is one of the most common chronic brain diseases, affecting more than 40,000 people in Ireland and 65 million people worldwide.

“By characterising and targeting an entire new class of molecules in epilepsy, we hope to develop innovative treatment strategies for temporal lobe epilepsy,” said Dr Gareth Morris, Marie Sklodowska-Curie Actions Fellow at FutureNeuro and Co-Lead Author of the paper.

Senior author on the study, Prof David Henshall, Director of FutureNeuro and Professor of Molecular Physiology and Neuroscience at RCSI added: “The discoveries here may be just the tip of the iceberg for new strategies in the treatment of epilepsy. I’m optimistic this can be translated to the clinic.”

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