Partnership for Pediatric Epilepsy Research

The Partnership for Pediatric Epilepsy Research is a consortium of epilepsy-related organizations and individuals working to encourage and support innovative research leading to new insights into pediatric epilepsy, its causes, and potential avenues for new treatments and cures. The consortium is supporting novel, investigator-initiated studies for pediatric epilepsies, specifically focused on increasing knowledge of causes, promoting innovative treatment approaches, and finding a cure for epilepsies that begin in infancy and childhood.

Current members include the American Epilepsy Society, the Epilepsy Foundation and Parents Against Childhood Epilepsy (P.A.C.E.). 

Recent Pediatric Research Awards

2009

Andrew Escayg, Ph.D. - Emory University

"Development of a high throughput assay to identify epilepsy mutations"

Genetic mutations are known to play an important role in the etiology of idiopathic generalized epilepsy (IGE), however the identification of the specific mutations that lead to IGE has been hampered by the high cost of traditional methods of DNA sequence analysis. We propose to develop a rapid and cost-effective method to screen genes for mutations in patients with epilepsy. This study would lead to much-improved DNA sequence-based clinical testing in epilepsy patients and the development of improved therapies that are based on a clearer understanding of the mechanism of epilepsy.

Jennifer S. Haut, Ph.D. - Cleveland Clinic Foundation

"Assessing reliable cognitive change in children following epilepsy surgery"

This study will develop reliable methods for assessing cognitive (i.e., intelligence, attention, memory) change in children with epilepsy. Using these methods, rates of cognitive change will be examined in pediatric patients who have undergone epilepsy surgery. This research will provide clinicians with the necessary tools to differentiate cognitive effects of epilepsy from cognitive effects of surgery. This information will help neuropsychologists inform parents and doctors about the cognitive risk associated with surgery and assist with prediction of overall learning and behavioral outcome. Furthermore, clinicians can use this information to more accurately identify cognitive and school abilities requiring intervention following surgery.

Jeanne Nerbonne, Ph.D. - Washington University in St. Louis

"Mechanisms linking SCN1B to neuronal excitability and pediatric epilepsies"

Voltage-gated potassium (Kv) channels are key determinants of neuronal excitability, and dysregulation of the functioning of these channels, resulting from inherited or acquired disease, has been linked directly to epilepsy. Recent studies have revealed an unexpected interaction between one of the prominent brain Kv channel proteins (Kv4.2) and Navbeta1 (SCN1b), an accessory subunit previously shown to be the locus of mutations that cause pediatric epilepsy. Previous studies have also demonstrated that young mice lacking Navbeta1 have fatal seizures. Here, we propose that epilepsy linked to SCN1b mutations (or to loss Navbeta1) reflects the loss of Kv4.2-encoded A-type Kv channels. The studies proposed here will provide new and fundamentally important insights into the physiological roles of Navbeta subunits in the regulation of neuronal Kv channels and neuronal excitability and into how mutations in Navbeta1 lead to pediatric epilepsy.
 

2008

Janelle Wagner, Ph.D. - Medical University of South Carolina

William R. Turk, M.D. Pediatric Epilepsy Research Award 

"Depression screening in youth with epilepsy"

Children with epilepsy are more likely to have depressive symptoms and thoughts of suicide.  However, depressive symptoms are often overlooked and these children do not receive mental health treatment. Thus, the proposed study addresses these problems by 1) revising an adult depression screening tool; 2) validating this depression screening tool; and 3) helping with access to mental health care providers for youth ages 12-17 with epilepsy.  In this study, youth and parents will complete written surveys and telephone interviews. Youth will be referred for mental health treatment as needed, and this process will be tracked.

Lori L. Isom, Ph.D. - University of Michigan

"Role of sodium channel SCN1B subunits in pediatric epilepsy"

Na+ channels regulate electrical activity in brain. Inherited disorders of Na+ channels cause epilepsy in humans. Mutations in ß1 (SCN1B) cause generalized epilepsy with febrile seizures plus type 1 (GEFS+1), a syndrome that displays multiple seizure types in different families. Epilepsy syndromes in GEFS+ families include febrile seizures, febrile seizures plus, mild generalized epilepsies, severe myoclonic epilepsy of infancy, temporal lobe epilepsy, and frontal lobe epilepsy. GEFS+ has also been identified in families bearing mutations in the Na+ channel a subunit gene SCN1A, as well as the GABAA receptor gene GABRG2. SCN1A, SCN1B, and GABRG2 may be functionally linked in the brain, as mutations in any of these genes can result in GEFS+. The goal of this research is to test the hypothesis that this epilepsy occurs through decreased Na+ current mediated by SCN1A channels  in GABAergic neurons. The results of this research will contribute to the understanding of the role of SCN1B in normal brain function as well as a greater understanding of how mutations in this gene lead to human pediatric epilepsy.      

Tianfu Li, Ph.D. - Legacy Research

"High neuronal adenosine kinase expression as risk factor for febrile seizure-induced epileptogenesis"

Prolonged febrile seizures during childhood are considered to be a major cause for the subsequent development of epilepsy. This project is based on findings that the brains’ own adenosine-based seizure control system is not yet fully developed during childhood. In particular, high levels of the adenosine removing enzyme adenosine kinase (ADK) appear to favor prolonged febrile seizures and subsequent epileptogenesis. This grant aims to identify high expression of ADK as a risk factor for febrile seizures and subsequent epileptogenesis, and to define ADK as a target for therapeutic intervention aimed at the prevention of epileptogenesis.                      

Anne Williamson, Ph.D. - Yale University

"Neuronal-glial metabolism in epileptogenic cortical malformations in patients"

Certain brain malformations can cause medically intractable seizures in children. The goal of this work is to use resected tissue from epileptic patients to obtain a metabolic signature for different types of malformations using a combination of neurochemical and imaging techniques.  These studies will allow us to better understand how different classes of cells interact biochemically in different types of epileptogenic tissue.  This work will help explain why certain types of malformations produce seizures as well as to identify new targets for therapy.

2006

Madison Berl, Ph.D. - Children's National Medical Center

“Working memory in children with epilepsy as assessed by functional imaging and neuropsychological studies”

Children with epilepsy often experience behavioral and cognitive difficulties. One area of difficulty is executive functioning which is a set of skills important for efficient task performance. This study characterizes the neural network of one aspect of executive functioning, namely working memory, and its impact on language in children with epilepsy using functional imaging and neuropsychological measures.

Linda K. Friedman, Ph.D. - New York College of Osteopathic Medicine (NYCOM) of New York Institute of Technology

“Age-dependent effects of seizures and antiepileptics on AMPA and mGluR receptors”

There is a critical lack of knowledge concerning what status epilepticus does to the developing brain. We question whether maturational changes in glutamate receptors occur after limbic seizures and whether antiepileptic treatment may alter these receptors in the presence or absence of seizures. Our questions are critical to pediatric epilepsy research because if seizures commence early in life, then over- or under-expression of glutamate receptors is either regulated in a cell- or age-specific manner. Thus, the age, timing of insults and type of antiepileptic drug administered appear critical to clinical outcomes.

Deanna S. Smith, Ph.D. — University of South Carolina

"Examining a post-developmental role for Lis1 in pediatric epilepsy"

Mutations in Lis1 inhibit events that occur during embryonic brain development and result in classical lissencephaly syndromes (smooth brain). Lis1 is also present in brain cells after birth and into adulthood. Defective Lis1 in older nerve cells may contribute to the increasingly severe seizures experienced by children with lissencephaly. This proposal will address the post-development role of Lis1 and may lead to a method to alleviate the seizures after birth.