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Study discovers three potential new targets for treating epilepsy

By Irish Pharmacist - 02nd Jul 2020

A major 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. 

The study was led by researchers at FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases, and the RCSI University of Medicine and Health Sciences. It is 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. The research is published in a recent issue of Proceedings of the National Academy of Sciences (PNAS) USA.

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 pharmacists 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 the RCSI, and co-lead author. “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.”

Epilepsy is one of the most common chronic brain diseases, affecting over 40,000 people in Ireland and 65 million people worldwide. There are more than 20 medicines available to prevent seizures in people with epilepsy, but progress has slowed in recent years and new treatments offer little benefit over those that have existed for decades.

“By characterising and targeting an entire new class of molecules in epilepsy, we hope to develop novel and 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. 

“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.”

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