Developing a new class of medications for epilepsy

Failure of modern ASMs to reduce the prevalence of drug-resistant epilepsy has been attributed to over-reliance on rodent models of acute seizures in drug development as they do not adequately recapitulate the mechanisms of human epilepsy. Our team has developed a novel in vitro ASM screening platform consisting of neuronal monolayers derived from human induced pluripotent stem cells. The model replicates the pharmacological effects of ASMs on neural activity as measured by a multi-electrode array. We will use our stem cell model to fast-track the development of a new class of ASMs that modulate adenosine A1 receptor (developed by our medicinal chemistry collaborators at Monash and published in Nature 2021). These compounds enhance the effect of adenosine which surges in response to seizure activity in the brain to stop the seizure. After optimisation for safety, metabolic stability and brain penetration, the lead compounds will progress to animal testing in our Neuroscience Laboratory.