Drug development

Over 70 million people worldwide suffer from epilepsy, with 90% of those cases taking place in developing countries (Singh & Trevick, 2016). Epilepsy can be defined as at least two unprovoked seizures occurring more than 24 hours apart, one unprovoked seizure with at least 60% chance of another seizure occurring within the next 10 years, or a diagnosis of epilepsy syndrome (Fisher et al., 2005). Varying physiological, molecular, genetic, and environmental factors can contribute to epileptic episodes. Although antiepileptic drugs (AEDs) exist, the complexity and lack of understanding behind the molecular mechanisms of the syndrome leaves the few drugs available to be insufficient for many patients (Rho & White, 2018). Therefore, the discovery of genetic pathways involved in epilepsy is imperative for the innovation of antiepileptic drugs. This thesis explores a novel method to add to mutant C.elegans libraries and improve antiepileptic drug discovery in a cost-effective and efficient manner by uncovering candidate molecular pathways through the candidate genes involved with antiepileptic strains.

Epilepsy is a widely prevalent disease within the United States. It is estimated that about 1.2% of the total American population has active epilepsy, a condition of the brain that causes seizures. These seizures are marked by chemical alterations in neuronal firing that can cause abnormal behavior, sensations, muscle spasms, and loss of consciousness. Although the prevalence of seizures and epilepsy is high, effective treatments are limited and fail to provide effective treatment for nearly one-third of adult epileptic patients. Here, I conclude results of successful screening of novel compounds that can ameliorate seizures using an electroshock assay to examine seizure susceptibility and duration in C. elegans. The use of this assay provides an excellent platform for novel antiepileptic drug (AED) discovery efficiently.
Literature shows Resveratrol, a natural product from plants, provides neuroprotective effects in various model organisms and therefore, is an excellent candidate for a molecule that has never been related to seizure. However, it is easily metabolized, being a flat and planar molecule. Our research group has collaboratively identified a novel bicyclic bridge molecule derived from the scaffolding of two resveratrol molecules we named Resveramorph (RVM). We also used the candidate approach to test a number of Resveramorph analogs on this assay to find the analog with highest efficacy. The various molecules characterized with their efficacy for seizure-like behavior after an electroshock have helped elucidate the mechanism of action and the RVMs physical target to give us greater insight into this potential family of AEDs.