SCIENCE: Study cracks code to treat epilepsy

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A major international study has uncovered three molecules that contain potential to be developed into new drugs to treat epilepsy. The disease is a chronic brain disease that affects 65 million people worldwide. They are prone to repeated seizures, but for the majority of people, these can be well controlled. 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 been around for decades.

According to the World Health Organisation (WHO), 70 percent of people with epilepsy can be seizure-free if they are properly diagnosed and treated, but about 80 percent of those affected by the disease are in low-income countries where healthcare system is poor.

But according to the study led by researchers at FutureNeuro, the SFI Research Centre for Chronic and Rare Neurological Diseases and RCSI University of Medicine and Health Sciences, the new findings are an important step towards discovering new drugs for people with epilepsy whose seizure cannot be controlled with current treatment.

The study is the result of seven years of research that involved contributions from 35 scientists based in eight different European countries across the field of neuroscience, genetics, computer science and synthetic chemistry.

The 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.

FutureNeuro Research Fellow and Co-Lead Author, Dr. Cristina Reschke said the group’s approach to drug discovery led to new types of molecules, “that can be targeted to prevent seizures with hopefully fewer side effects. 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.”

Another co-lead author of the study, Dr. Gareth Morris, described the development as 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. “By characterizing and targeting an entire new class of molecules in epilepsy, we hope to develop novel and innovative treatment strategies for temporal lobe epilepsy,” he said.

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