Prevention of Temporal Lobe Epilepsy

点击翻译按钮获取中文摘要

DESCRIPTION (provided by applicant): Limbic epilepsy is a common and frequently devastating disorder for which there is no prevention or cure, except for surgery for a minority of individuals. Status epilepticus (SE) has been implicated as a key etiological event in development of limbic epilepsy. Studies of animal models using genetically modified mice suggest that limiting activation of the receptor tyrosine kinase, TrkB, will prevent development of spontaneous recurrent seizures arising as a consequence of limbic SE. We have discovered a peptide that limits TrkB signaling in vitro and following systemic administration in vivo. Aim 1 wil determine the optimal dose and time course of efficacy and pharmacokinetic properties of this peptide; mice will be treated with varying doses and at varying intervals prior to induction of kainic acid-induced SE. Aim 2 will determine whether one week of treatment with the peptide commencing 40 minutes after onset of kainic acid-evoked SE will prevent SE-induced spontaneous recurrent seizures. Successful completion of these Aims will provide proof of concept of efficacy of this peptide for SE-induced epileptogenesis and provide the basis of a UO1 application aimed at pharmacological optimization of this peptide.