Featuring the work of former CURE Grantee Dr. David Henshall
Summary, published by the Royal College of Surgeons in Ireland
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 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 the current issue of Proceedings of the National Academy of Sciences (PNAS).
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, synthesized 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. “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.”