The tragedy of epilepsy emerges from the combination of its high prevalence and impact upon patients and their families. Childhood epilepsies are typically severe, often presenting in infancy with pharmaco-resistant seizures. These are thought to contribute to developmental disabilities and debilitating comorbidities commonly present in these patients. In addition, there is an increased risk of sudden unexpected death in epilepsy or SUDEP in these populations. Despite the availability of multiple antiepileptic drugs (AED), approximately one third of epilepsy patients still experience pharmaco-resistant seizures, representing a significant unmet medical need. New therapies with a differentiated mechanism of action are desperately needed. Neuroactive steroids (NAS) are a family of steroid based compounds of both natural and synthetic origin, which display an array of central nervous system (CNS) activities, including the modulation of the GABAA and NMDA receptor systems. As the primary inhibitory neurotransmitter in the nervous system, GABA influences the activity of neural circuits governing brain states and behaviors, including mood, anxiety, seizures and sleep. The neuroactive steroid, SGE-516, is a positive allosteric modulator of both gamma- and delta subunit containing GABAA receptors. This broad GABAA receptor activity differentiates neuroactive steroids like SGE-516 from benzodiazepines, a class of anticonvulsants which have been shown in vitro to selectively target gamma-subunit containing GABAA receptors. This presentation will highlight the medicinal chemistry efforts towards the discovery of SGE-516 and other neurosteroids for the treatment of epilepsy.

Novel synthetic neurosteroids to reduce seizure burden and improve survival in preclinical models of catastrophic epilepsies

2019 Fall National Meeting

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.