Preclinical research on novel therapies and neurochemistry in intractable epilepsy

Abstract

Epilepsy is a condition involving underlying hyperexcitability of neurons in the brain leading to various seizure-related phenotypes. However, there remains unmet clinical need in epilepsy for around 30% of patients that remain resistant to treatment. This requires new therapeutic targets to be explored, through the characterization of novel neurochemical pathways that respond to seizures and testing novel candidate molecules for anti-seizure effects in state-of-the-art preclinical models of seizures.

Cannabidiol (CBD), a non-psychoactive cannabinoid derived from Cannabis sativa, displays promising anti-seizure effects in patients of Dravet syndrome and Lennox-Gastaut syndrome, two types of epilepsy that are resistant to current medications. The chemical structure of CBD provides a scaffold for developing novel anti-seizure agents. Additionally, this has led to further investigations into the role of the endogenous cannabinoid system and other lipid-related signaling pathways in epilepsy and whether these systems could be leveraged to develop new anti-seizure drugs. The present thesis then aimed to further advance this field of research by identifying novel cannabinoid-related anti-seizure agents and investigating the impact of seizures on the novel lipid signaling mediators called the specialized pro-resolving mediators which assist in brain repair.