PEOPLE AGAINST CHILDHOOD EPILEPSY, INC.
A Research and Education Fund
The Partnership for Pediatric Epilepsy Research is a consortium of epilepsy-related
organizations and individuals committed to support of research into the causes, treatment and
eventual cure of childhood epilepsies.
Current members include the American Epilepsy Society, the Epilepsy Foundation, Derek's Fund,
Finding A Cure for Epilepsy and Seizures(f.a.c.e.s.), Epilepsy Cure Project, and People
Against Childhood Epilepsy (P.A.C.E.).
Partnership for Pediatric Epilepsy Research
Click here for the PPER Special Research Grants Program application and information.
- Jeanne Nerbonne, Ph.D.
Washington University in St. Louis
Mechanisms linking SCN1B to neuronal excitability and pediatric epilepsies
Summary: 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
- Andrew Escayg, Ph.D.
Development of a high throughput assay to identify epilepsy mutations
Summary: 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
Summary: 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 as
sist 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.
- Janelle Wagner, Ph.D.
Medical University of South Carolina
Depression Screening in Youth with Epilepsy
Summary: Children with epilepsy are more lkely 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 10 revising an adult depression screening tool; 20 validating this depression screening tool; and 3) helping with access to mental health
care providers for youths 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 Isom, Ph.D.
University of Michigan
Role of sodium channel SCN1B subunits in pediatric epilepsy
Summary: Na+ channels regulate electrical activity in the brain. Inherited disorders of Na+ channels cause epilepsy in humans.
Mutations in B1 (SCN1B) caise 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 included 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 wel as the GABAA receptor gene GABRG2, SCN1A, SCNiB, and GABRG2 may be
functionallylinked in the brain, as mutations in any of these genes can result in EFS+. The goal if this research is to test the hypothesis
that this epilepsy occrs through decreased Na+ current mediated by SCN1A channels in GAGAergic neurons. The results if 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, Postdoctoral Fellow
High neuronal adenosine kinase expression as risk factor for febrile seizure-induced epilepstogenesis
Summary: Prolonged febrile seizures during childhood are considerd 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 epilepstogenesis. This grant aims to identify high expression of ADK
- Anne Williamson, Ph.D.
Neuronal-Glial metabolism in epileptogenic cortical malformations in patients
Summary: Certain brain malformationscan cause medically intractible seizures in children. The goal of this work is to use
resected tissue from epilepstic patients to obtain a metabolic signature for different types of malformations using a combination of
neurochenical 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 produced seizures as well as to
identify new targets for therapy.
Spring 2006 Grants
- Deanna S. Smith, Ph.D.
University of South Carolina
Examining a post-developmental role for Lis 1 in pediatric epilepsy
Summary: Mutations in Lis 1 inhibit events that occur during embryonic brain development and result in classical lissencephaly
syndromes (smooth brain). Lis 1 is also present in brain cells after birth and into adulthood. Defective Lis 1 in older nerve cells may
contribute to the increasingly severe seizures experienced by children with lissencephaly. Thei proposal will address the post-development
role of Lis 1 and may lead to a method to allieviate the seizures after birth.
- 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
Summary: There is a critical lack of knowledge concerning what status epilepsticus 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.
- Madison Mehalani Berl, Ph.D.
Children's National Medical Center
Working memory in children with epilepsy as assessed by functional imaging and neuropsychological studies
Summary: 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
- Ann Elizabeth, Anderson, M.D.
Baylor College of Medicine
Activity-dependent ion channel regulation: A candidate mechanism in developmental epilepsy
Summary: Ion channel gene defects have been identified in some forms of epilepsy; however, the underlying cause of the majority
of epilepsies remains undefined. We will test whether prolonged seizures early in life causes long-lasting changes in ion channels and
whether this has a consequence on the development of seizures later in life.
- Gregory Neal Barnes, M.D., Ph.D.
Vanderbilt University Medical Center
Anti-epileptic agents & synaptic reorganization - semaphorin signaling in developing hippocampal excitatory synapses
Summary: Excessive electrical activity during childhood status epilepticus may trigger a re-wiring of the developing brain
leading to a maladaptive neuronal connections and acquired epilepsy. This study will investigate a molecular cue, named 3F signaling, which
plays a critical role in hippocampal circuitry formation and epileptogenesis. The goal of this research is to develop treatments to disrupt
the formation of aberrant synapses and brain circuitry, thereby preventing epilepsy and behavioral disturbances in brain injured children.
- Jennifer A. Kearney, Ph.D.
University of Michigan
Positional cloning of an epilepsy modifier gene
Summary: The goal of this project is to identify a gene that influences epilepsy susceptibility and clinical severity.
Identification of genes that influence disease susceptibility and progression will provide insight into the biological basis of epilepsy and
will contribute to identifying pediatric patients who are at risk for developing epilepsy.
- Sookyong, Koh, M.D., Ph.D.
Children's Memorial Hospital
Gene therapy in childhood epilepsy
Summary: Memory impairment, school failure and behavioral problems are common among children with epilepsy and often become
the central focus for many families. The aim of this proposal is to use gene therapy to ameliorate seizure-induced memory and behavioral
deficits in an animal model of childhood epilepsy.
Grants that began on December 1, 2004
- Brenna McDonald Psy.D., Andrew Saykin Psy.D and Gregory Holmes M.D.
Dartmouth Medical School
Anatomical Localization of Memory Using Novel fMRI Paradigms in Children with Epilepsy
Summary: This study will validate functional MRI memory tasks for young
children, and will compare the brain activation patterns in children with epilepsy to healthy
controls. This data may help lead to the replacement of the intracarotid amobarbital test (IAT)
with MRI in surgical planning, resulting in improved treatment for children with epilepsy.
- Gregory Kinney Ph.D.
University of Washington
Developmental Regulation of Tonic GABAergic Inhibition
Summary: Evidence suggests that elevation of inhibitory neurotransmitter levels
can result in activation of or enhancement of a slow, tonic inhibition, indicating that
activation of this form of inhibition may underlie the effects of drugs that alter inhibitory
neurotransmitter levels. However slow, tonic inhibition may not be fully developed in young
tissue; consequently, the developing brain may be more susceptible to seizure generation.
This proposal will investigate the presence and function of slow, tonic inhibition
during different stages of development.
- Dane Chetkovich M.D., Ph.D.
Northwestern University, Feinberg School of Medicine
Role of the HCN2 Ion Channel in Epilepsy
Summary: This proposal characterizes the molecular changes underlying epilepsy
in a mutant mouse strain named "apathetic", which is affected with ataxia, myoclonic seizures,
and progressive loss of interaction with the environment, and as such is a new animal model for
Severe Myoclonic Epilepsy of Infancy (SMEI).
- George Hess, Ph.D.
Mechanism of Action of Pyrrolidin-2-one Anticonvulsants
Summary: This Project aims to elucidate the molecular mechanism of action of a
promising class of anticonvulsants, which includes levetiracetam (Keppra) and diethyl-lactam.
This mechanism is presently unknown. Newly developed biophysical techniques will be used to solve
this problem. The knowledge gained will aid in the rational design of improved antiepileptic
medication for both children and adults.
- Karen Gale, Ph.D.
Georgetown University Medical Center
Impact of Repeated Seizures and Anticonvulsant Treatment on Neuronal Survival in the Immature Brain
Summary: Seizures in childhood may impede the natural elimination of excess
neurons. Conversely, certain antiepileptic drugs can trigger neuronal death during early infancy.
This study will examine the cellular and behavioral effects of recurrent seizures and drug
treatments in infant rats in order to determine how adverse long-term outcomes may be avoided in
the course of antiepileptic therapy for infants. The results will have important implications for
seizure treatment strategies in childhood in order to minimize adverse developmental outcomes.
Grants that began on August 1, 2003
- Mark A. Tanouye, Ph.D.
University of California, Berkeley
Development of Human Anti-epileptic Drug Therapy Using a Drosophila Model
Summary: The application proposes to use Drosophila as a model organism to
investigate novel genetic approaches to the treatment of seizures.
- John W. Swann, Ph.D. and Michael Sheldon, Ph.D.
Baylor College of Medicine
Seizure-induced Learning Deficits: Molecular Mechanisms
Summary: This project is to study the mechanisms of NMDA receptor
down-regulation in hippocampal slice cultures, following chronic exposure to bicuculline (BIC).
They propose to use molecular techniques to dissect the pathway(s) whereby chronic BIC exposure
leads to shut-off of the transcription factor CREB.
- Tracy A. Glauser, M.D.
Cincinnati Children's Hospital Medical Center
Pharmacogenetics of Antiepileptic Drug Metabolism and Neurological Toxicity in Children with
Summary: The investigators propose that inter-individual variability in
pharmacokinetics and neurologic toxicity due to VPA and CBZ are due to polymorphisms in drug
- Pratik Mukherjee, MD Ph.D.
University of California, San Francisco
Diffusion Tensor Magnetic Resonance Imaging for the Improved Presurgical Evaluation of Partial
Summary: This study would test the value of DT-MRI (Diffusion Tensor Magnetic
Resonance Imaging) for identifying cortical malformations causing epilepsy in children.
- K. Michael Gibson, Ph.D., FACMG
Oregon Health & Science University
Murine Succinate Semialdehyde Dehydrogenase Deficiency, an Epileptic Disorder with Elevated
Summary: The central goal of this proposed research is to extend the ongoing
analyses of the pathogenic mechanisms that lead to seizures in the mouse knockout of the
Succinate Semialdehyde Dehydrogenase (SSADH) gene.
- Deb K. Pal, Ph.D., Martina Durner, M.D. and David Greenberg, Ph.D.
Multicenter Family Study of Rolandic Epilepsy
Summary: The proposal is based upon the supposition that gene(s) discovery for the
complex epilepsies (i.e. Rolandic epilepsy) will require collection of DNA from large
populations of individuals whose phenotypes have been rigorously characterized. The applicant
proposes to collect approximately 50 individuals and 25 families with RE during the 2 years,
administer a standardized questionnaire, obtain an EEG and blood for DNA extraction.
- Dennis J. Dlugos, M.D. and Brian Litt, M.D.
Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine
Characterization of Seizure Precursors in Childhood Extra-Temporal Epilepsy
Summary: There is new evidence that EEG can be used to predict seizures before they
occur. This study will use tools from the engineering world to predict seizures before they
occur in children with difficult-to-control epilepsy beginning outside of the temporal lobe.
This work will make an important contribution to efforts which hopefully lead to an implantable
device to predict and prevent seizures.
- Paul R. Carney, M.D., J. Chris Sackellares, M.D., Deng Shiau, Ph.D. and Panos Pardalos, Ph.D.
University of Florida
A Quantitative EEG Method for "Real-Time" Detection of Neonatal
Seizures in the Neonatal Intensive Care Unit
Summary: The overall goal of this research is to develop an automated brain
monitoring system that can be employed at the bedside in order to assist health professionals
with a user-friendly method for evaluating newborns at risk for seizures. We will bring a
comprehensive knowledge of neonatal epilepsy, recordings from an extensively evaluated and
characterized newborn population, a non-prejudiced application of powerful linear and nonlinear
methods, and a strong theoretical rationale for these methods to bear on the problem of newborn
Grants that began on June 1, 2002
- Richard M. Myers, Ph.D.
Stanford University School of Medicine
Studies to define the pathogenic mechanisms of seizures in Unverricht-Lundborg Progressive
Myoclonus Epilepsy (EPM1)
Summary: Analysis of samples from patients diagnosed with the Unverricht-
Lundborg type of childhood epilepsy has proven that the cystatin B molecule is missing in this
disease. Why the body requires this protein in unknown. The consequences of decreased cystatin
B will be studied by using experimental mice that have been engineered not to make the cystatin
- Manisha N. Patel, Ph.D.
National Jewish Medical and Research Center
Role of Mitochondrial Superoxide in Seizure Susceptibility
Summary: Childhood seizure disorders can result from conditions such as hypoxia,
trauma, and inherited defects, which can increase the production of oxygen radicals. Using
genetically altered mice, this proposal will determine whether increased formation of oxygen
radicals can produce seizures. This knowledge can lead to novel therapies for the treatment of
- Steven N. Roper, M.D.
University of Florida College of Medicine
Function of Inhibitory Interneurons in Experimental Cortical Dysplasia
Summary: Cortical dysplasia is a major cause of epilepsy that cannot be controlled
with medications and, in some cases, this appears to be due to an impairment of inhibition in the
affected neurons. This study will use a mouse model to directly study the function of
inhibitory interneurons in cortical dysplasia.
- Renato Rozental, M.D., Ph.D. & Solomon L. Moshe, M.D.
Albert Einstein College of Medicine of Yeshiva University
Following Perinatal Hypoxic-Ischemic Insults on the Extent of Delayed Neurotoxicity
Summary: Neonatal seizures most frequently accompany hypoxic-ischemic insults and
may damage the developing brain. Using a multidisciplinary approach, this study seeks to
determine, in neonatal rats following intrauterine transient global ischemia, whether blockade of
gap junction channels may prevent seizures and seizure-induced delayed neuropathologic damage.