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.

Public Health Relevance

Temporal lobe epilepsy is a common and commonly devastating form of human epilepsy for which there is no method of prevention. The proposed studies seek to establish proof of efficacy for a small peptide for prevention of epilepsy in an animal model.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21NS078259-02
Application #
8554922
Study Section
National Institute of Neurological Disorders and Stroke Initial Review Group (NSD)
Program Officer
Whittemore, Vicky R
Project Start
2012-09-30
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
2
Fiscal Year
2013
Total Cost
$184,316
Indirect Cost
$63,691
Name
Duke University
Department
Biology
Type
Schools of Medicine
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705