Three Potential Targets for New Epilepsy Treatments

A study published yesterday in PNAS has uncovered three molecules that could potentially be developed into 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 researchers identified and measured levels of over a billion microRNAs to investigate whether they were changed in epilepsy. In so doing, they discovered a small set of microRNAs that were always elevated in epilepsy, and they designed and synthesized drug-like molecules to target them. 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, which is part of the brain’s immune system and 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,” says coauthor Cristina Reschke of RCSI. “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. People with epilepsy 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.

“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,” says coauthor Gareth Morris, also of RCSI. “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.”