New experimental therapies for status epilepticus in preclinical development

Matthew Walker, Robin Williams

Research output: Contribution to journalLiterature reviewpeer-review

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Abstract

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.
Original languageEnglish
Pages (from-to)290–293
Number of pages4
JournalEpilepsy and Behaviour
Volume49
Early online date17 Jul 2015
DOIs
Publication statusPublished - Aug 2015

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