TY - JOUR

T1 - New experimental therapies for status epilepticus in preclinical development

AU - Walker, Matthew

AU - Williams, Robin

PY - 2015/8

Y1 - 2015/8

N2 - Starting with the established antiepileptic drug valproic acid, we have taken a novel approach to develop new antiseizure drugs that may be effective in status epilepticus. We first identified that valproic acid has a potent effect on a biochemical pathway, the phosphoinositide pathway, in Dictyostelium discoideum and we demonstrated that this may relate to its mechanism of action against seizures in mammalian systems. Through screening in this pathway, we have identified a large array of fatty acids and fatty acid derivatives with antiseizure potential. These were then evaulated in an in vitro mammalian system. One compound that we identified through this process is a major constituent of the ketogenic diet, strongly arguing that it may be the fatty acids that are mediating the antiseizure effect of this diet. We further tested two of the more potent compounds in an in vivo model of status epilepticus and demonstrated that they were more effective than valproate in treating the status epilepticus.

AB - Starting with the established antiepileptic drug valproic acid, we have taken a novel approach to develop new antiseizure drugs that may be effective in status epilepticus. We first identified that valproic acid has a potent effect on a biochemical pathway, the phosphoinositide pathway, in Dictyostelium discoideum and we demonstrated that this may relate to its mechanism of action against seizures in mammalian systems. Through screening in this pathway, we have identified a large array of fatty acids and fatty acid derivatives with antiseizure potential. These were then evaulated in an in vitro mammalian system. One compound that we identified through this process is a major constituent of the ketogenic diet, strongly arguing that it may be the fatty acids that are mediating the antiseizure effect of this diet. We further tested two of the more potent compounds in an in vivo model of status epilepticus and demonstrated that they were more effective than valproate in treating the status epilepticus.

U2 - 10.1016/j.yebeh.2015.06.009

DO - 10.1016/j.yebeh.2015.06.009

M3 - Literature review

VL - 49

SP - 290

EP - 293

JO - Epilepsy and Behaviour

JF - Epilepsy and Behaviour

ER -