CURE - Citizens United for Research in Epilepsy It's Time We Found a CURE CURE Epilepsy Research

CURE’s mission is based on the fact that research is the key to finding cures for the epilepsies. Each year, grants are funded based on promising trends in the field and the potential for breakthroughs in a specified area. The below grant recipients were selected with the invaluable assistance of the CURE Scientific Advisory Council, the Lay Review Council, and the scientific peer reviewers who generously volunteer their time to CURE.

See previous years: 2013  |  2012  |  2011  |  2010  |  2009  |  2008  |  Older


Challenge Awards
Two- to three-year grants up to $250,000 for established investigators or early career investigators exploring cutting-edge approaches to curing epilepsy.

CURE grant award CJM Foundation Award
Norwood

Braxton Norwood, PhD
Phillips Universitaet Marburg, Germany

“Endosomal Toll-Like Receptor (eTLR) Targeting to Prevent/Treat Epilepsy: In Vivo Proof-of-Concept”

Epilepsy is a complex disorder that is controlled by many factors. Toll-like receptors (TLRs), part of the immune system, play a crucial role in the development of epilepsy, regulating many processes that are altered in this disorder. We recently discovered that mice with particular TLR dysregulation exhibit spontaneous seizures in adulthood, despite having normal brain structure. We hypothesize that this immune system dysfunction causes epilepsy. We will first characterize this novel model of epilepsy and then determine whether manipulating these TLRs, with commercially available substances, can stop/prevent epilepsy. The resulting translational data could lead to novel therapies for epilepsy.



CURE grant award Madison Friends of CURE Award
Schaefer

Anne Schaefer, MD, PhD
Icahn School of Medicine at Mt. Sinai

“Non-coding RNA-mediated control of neuronal excitability and epilepsy.”

Human and animal behavior depends on the tight balance between excitatory and inhibitory signals that arise within neurons in the brain. Epilepsy occurs when the excitatory signals take over, either due to aberrant activity of excitatory neurons or malfunction of inhibitory neurons. Our proposal aims to curb excessive excitatory signals during epilepsy. We found that a single brain-expressed small RNA, which represents a family of the so-called microRNAs, is capable of controlling neuronal excitability. Our experiments revealed the ability of the microRNA miR-128 to govern motor behavior and to prevent seizures induced by various factors. The advantage of microRNAs is that they can be formulated relatively easily into a therapy. Both microRNAs as well as microRNA antagonists can potentially be used to modulate the activity of neurons. Our aim is to use miR-128 or its antagonists to suppress pathological neuron excitation causing fatal epilepsy in mice, and to extend our findings to further advance human epilepsy treatment.





Prevention of Acquired Epilepsies Awards
Two-to three-year grants up to $250,000 in support of research relevant to the prevention and treatment of acquired (post-insult) epilepsies.

Lin-Fletcher-Xu

Xiaoming Jin, PhD
Fletcher White, PhD
Zao Xu, MD, PhD

Indiana University School of Medicine

“Targeting High Mobility Group Box-1 Signaling for Preventing Posttraumatic Epileptogenesis”

Brain injuries or seizures cause the damaged brain cells to release high mobility group box-1 (HMGB1), a protein that binds to its receptors (including TLR4) and plays a central role in inducing inflammation, brain damage, and abnormal brain activity. In this project, we will use an animal model to determine brain injury-induced changes in HMGB1 and its receptors and their contribution to the development of epilepsy. We will also directly test whether neutralizing HMGB1 will prevent posttraumatic epilepsy. Because targeting HMGB1 may promote brain repair and can be achieved with several currently available drugs or molecules, this strategy may have great potential for clinical application.



Kaufer-Friedman

Daniela Kaufer, PhD
The Regents of the University of California, Berkeley

Alon Friedman, MD, PhD
Dalhousie University & Ben-Gurion University

“Transforming Growth Factor Beta Signaling Following Traumatic Brain Injury as a Target for the Prevention of Acquired Epilepsy”

Currently, there are no biomarkers that reliably predict patients at-risk to develop epilepsy after traumatic brain injury (TBI), nor interventions for preventing the development of post-traumatic epilepsy (PTE). We previously demonstrated the critical role of blood-brain barrier dysfunction, serum albumin, and the activation of inflammatory transforming growth factor beta (TGF-ß) signaling in PTE. Here we will monitor BBB dysfunction and test the efficacy of TGF-ß signaling blockers in preventing PTE in a rodent PTE model. Our ultimate goal is to develop a clinical protocol that will identify patients with BBB dysfunction, prior to the onset of epilepsy, and accordingly individualize a preventive therapeutic intervention.



CURE grant award Brighter Future Award
Sutula

Thomas Sutula, MD, PhD
University of Wisconsin, Madison

“IND-Enabling Preclinical Studies of 2DG for Prevention of Post-Traumatic Epilepsy in Plasticity-Susceptible Rats”

Post-traumatic epilepsy is a major cause of ongoing and progressive morbidity in survivors of traumatic brain injury (TBI) which afflicts as many as 1.7 million people in the US each year. Overall, PTE accounts for nearly 20% of all symptomatic epilepsies in the general population, and is the most common cause of acquired epilepsies. This project is addressing this significant need by determining if administration of 2DG, a novel sugar analogue that blocks sugar metabolism, at the time of TBI reduces or prevents later development of post-traumatic epilepsy. Successful completion of this project will enable rapid advance of 2DG into clinical trials to reduce or prevent post-traumatic epilepsy, which would be an unprecedented advance toward the goal of “no seizures, no side effects” by preventing this most common cause of acquired epilepsy.





SUDEP (Sudden Unexpected Death in Epilepsy) Awards
One-year grants up to $100,000 in support of innovative studies that will provide new directions for SUDEP research.

CURE grant award Christopher Donalty and Kyle Coggins Award
Kalume

Franck Kalume, PhD
Seattle Children’s Research Institute

“A Comparative Study of Sudden Unexpected Death in Mouse Models of Focal Cortical Dysplasia and Dravet Syndrome”

Sudden unexpected death in epilepsy (SUDEP) is the most common cause of death in people with treatment-resistant epilepsies. But, its mechanisms are not completely understood. Such life-threatening epilepsies include epilepsy associated with Focal Cortical Dysplasia (FCD) and Dravet syndrome (DS). FCD is developmental disorder marked by abnormal formation of the cerebral cortex. It has been recently associated with mutations in PIK3CA gene. DS is a severe pediatric epilepsy, with one of the highest rates of SUDEP. DS is caused by mutations in SCN1A gene. In recent studies, we found that SUDEP of our mouse model of DS occurs when a severe seizure causes hyperactivity of the vagus nerve, which is immediately followed by prolonged bradycardia and ventricular dysfunction. In the studies proposed in this research project, we will use our DS mouse model and a recent mouse model of FCD to examine whether there is a common mechanism of sudden unexpected death in these two types of epilepsy. We will conduct experiments to Identify and compare the cardiac, respiratory, and post-seizure brain activity changes that predict SUDEP susceptibility in DS and FCD mice. In addition, we will characterize and compare the neuronal circuits that mediates these SUDEP-related physiological anomalies.



CURE grant award The Henry Lapham Memorial Award
Bateman & Schevon

Lisa Bateman, MD
Catherine Schevon, MD, PhD

Columbia University Medical Center

SUDEP Risk and Biomarkers in the Surgical Epilepsy Population

Patients considering epilepsy surgery are at high risk for SUDEP. Lowering SUDEP risk is often a motivation for undergoing surgery, but even patients thought to be seizure-free after surgery have suffered from SUDEP. We will study records of patients evaluated for epilepsy surgery at our center spanning almost twenty years to determine whether surgery indeed reduces SUDEP incidence and whether factors besides seizure outcome may predict SUDEP risk. These include where seizures start and spread, features of seizure recovery, and effects of seizures on heart and breathing function. It is hoped that the information learned from this study will lead to an increased understanding of individual SUDEP risk prediction and help to guide patients and their doctors in making clinical care decisions related to epilepsy surgery.





Pediatric Epilepsies Awards
2-year grants up to $250,000 in support of research projects of relevance to the numerous debilitating and difficult to treat pediatric epilepsies

Catterall & Westenbroek

Ruth Westenbroek, PhD
William Catterall, PhD

University of Washington

“Mechanism of Anti-Epileptic Action of Cannabidiol in a Mouse Model of Dravet Syndrome”

Life-threatening pediatric epilepsies such as Dravet Syndrome (DS) are unresponsive to standard therapies. Marijuana could have therapeutic benefit but some evidence suggests the psychoactive component, Δ9-tetrahydrocannabinol, might cause cognitive and behavioral toxicity in children. Animal and human studies suggest that the nonpsychoactive compounds cannabidiol (CBD) and cannabidivarin (CBDV) are responsible for the antiepileptic effects of marijuana; however, little is known about the how CBD/CBDV function. We will study the effects of CBD/CBDV on seizures, premature death, and cognitive deficits in a well-validated mouse genetic model of DS, and we will determine the process responsible for their therapeutic effects.



Benfenati

Laura Jansen, MD, PhD
University of Virginia

“Identification of Novel Therapies for Intractable Pediatric Epilepsy due to the Cortical Dysplasias”

Cortical Dysplasia, a type of brain malformation, is a common and understudied cause of childhood epilepsy. Seizures due to cortical dysplasia frequently do not respond to currently used anti-seizure medications, making it the most common reason for epilepsy surgery in childhood. Many cortical dysplasias are associated with abnormal activity of a signaling chain of events that occurs inside neurons. This specific chain of events is called the PI3K/AKT signaling pathway. In this project, we will combine studies of surgically-resected human brain specimens with those of a patient-specific neuronal culture model in order to examine the effects of medications that inhibit this pathway. Our ability to test potential therapies directly on tissue from an affected child as well as on neurons expressing the same genetic mutation as that child will pave the way for the application of "personalized medicine" techniques to the treatment of intractable pediatric epilepsy.



CURE grant award New York Friends of CURE Pediatric Epilepsy Award in Memory of Danny Tromberg
Rossignol

Elsa Rossignol, MD, MSc
Université de Montréal, CHU Ste-Justine, Canada

“GABAergic Interneuron Migration Impairments in Epileptic Encephalopathies”

The epileptic encephalopathies are severe childhood disorders characterized by epilepsy with developmental delay and/or intellectual disability. These disorders were largely unexplained until recently. Improved genomic techniques have now allowed us to identify new genes involved in these disorders. However, the functions of these genes remain unknown. We study the roles of these genes during the development of inhibitory neurons that are essential to prevent excessive brain excitation and seizures. For this purpose, we use a combination of genetic techniques and imaging in embryonic mice brains and investigate the way inhibitory interneurons migrate and mature. These experiments will help us clarify the mechanisms by which mutations in these new genes cause epilepsy and will help develop better therapies for children with epileptic encephalopathies.





Innovator Awards
One-year grants up to $50,000 in support of the exploration of a highly innovative new concept or untested theory that addresses an important problem relevant to epilepsy

CURE grant award 2014 CURE 365 Innovator Award
Benfenati

Fabio Benfenati, MD
The Italian Institute of Technology

“Optogenetic Regulation of the Transcription of Epilepsy Genes: an Innovative Strategy to Cure Drug-Resistant Epilepsy”

Epilepsy can be caused by a number of environmental and pathological factors. Regardless of the specific cause, however, the ultimate effect is an alteration of the mechanisms that modulate the normal functioning of our brain, which then becomes “hyperexcitable”. We have engineered a novel therapeutic approach based on the generation of artificial molecules that can turn off specific pathological processes in the sick brain. We aim at delivering such molecules to the brain in order to “switch off” the pathogenic pathways that would lead to the onset of seizures, and actively maintain control of excitability until the physiological state of the brain is recovered.



Roopra

Avtar Roopra, PhD
University of Wisconsin-Madison

“Targeting Epigenetics to treat Epilepsy in Tuberous Sclerosis Complex: An Epiphany From Patient Whole Genomic Expression Analysis”

Epilepsy has both genetic and non-genetic roots and Tuberous Sclerosis Complex (TSC) is a leading genetic cause. Though much is understood about the mutations behind TSC, nothing is known about the drivers of gene changes in the brains of TSC patients that cause seizures and epilepsy. The work proposed here is the first to explore alterations in the way genes are controlled, a process called ‘epigenetics’ that we believe is a major driver of epilepsy in TSC. We aim to open up an entirely new arsenal of drugs – epigenetic modifiers - in the fight against epilepsy in TSC. TSC associated genes play a role in almost every model of epilepsy. Therefore we believe that our finding will aid in the quest for “no seizures, no side effects” in multiple genetic and non-genetic epilepsies.



Sundaram

Senthil Sundaram, MD
Wayne State University

“Identification of Aberrant Gene Regulatory Networks in Infantile Spasms”

The goal of this study is to identify abnormal gene regulatory networks (GRN) of infantile spasms by leveraging the recent advances in genetic research. These advances allow us to creatively utilize the scarce surgical brain tissue obtained in our center over the years from children with infantile spasms. The construction of GRN will enhance our understanding of the mechanisms by which the disease develops. In addition, this knowledge can be used to identify new drug targets. If FDA-approved drugs are already available for these new targets, new clinical trials can be started to determine whether they are useful in treating infantile spasms. If such FDA-approved drugs are not available for these targets, the knowledge obtained from this study can be used to initiate new drug discovery programs. Thus, we believe that the results of this study could potentially open up new possibilities for therapeutic intervention.




Taking Flight Awards
One-year grants up to $100,000 to help promote the careers of young investigators and support them as they develop an independent research focus

Ethan Goldberg

Ethan Goldberg, MD, PhD
The Children’s Hospital of Philadelphia

“Treatment of temporal lobe epilepsy in a rodent model using subtype-specific cortical interneuron precursors”

New strategies for the treatment of medically intractable epilepsy are desperately needed. Cell-based transplantation is slowly emerging as a real therapeutic possibility, although many barriers remain. Dr. Goldberg proposes to use specific, defined subtypes of cortical interneuron precursors to treat epilepsy and its comorbidities in an experimental model of acquired chronic temporal lobe epilepsy. They will assess the functional integration of transplanted interneurons into normal and epileptic hippocampus as well as the ability of such cells to correct circuit-level dysfunction seen in epileptic brain circuits. They will also test the efficacy of transplanted cells in reducing or eliminating seizures in this preclinical model.



Catherine Christian, PhD

Catherine Christian, PhD
University of Illinois at Urbana-Champaign

“Modulation of GABAergic Transmission and Absence Seizures by Optical Stimulation of Astrocytes”

Synaptic inhibition between neurons in the thalamic reticular nucleus (nRT) plays a critical role in childhood absence epilepsy. Dr. Christian’s recent work has demonstrated that astrocytes, a type of non-neuronal brain cell, play a necessary role in regulating inhibition in the nRT. This suggests the exciting prospect that modulation of astrocytic function, and thereby of synaptic inhibition, could become a powerful resource in treating seizure disorders. The proposed studies will focus on using newly developed methods to selectively stimulate astrocytes in the nRT using light, and assess the effects of this stimulation on both synaptic inhibition and absence seizures.



Krook-Magnuson

Esther Krook-Magnuson, PhD
University of California, Irvine

“On-demand restoration of the dentate gate for temporal lobe epilepsy”

This work seeks to identify a new target for intervention to inhibit temporal lobe seizures, with the goal of effectively controlling seizures while minimizing side-effects through greater specificity of intervention. Optogenetics is a powerful technology allowing selective control of specific populations of brain cells at specific times using light. This project uses a mouse model of temporal lobe epilepsy to investigate whether a responsive optogenetic intervention applied only when a seizure occurs and selectively targeting only a subset of excitatory cells in the temporal lobe can control spontaneous temporal lobe seizures. It further investigates the cognitive benefits of this temporally, spatially, and cell-type selective intervention.



CURE grant award Grants marked with an asterisk are made possible by individuals, families, foundations, or corporations.



 

See previous years' CURE grant recipients:
2013  |  2012  |  2011  |  2010  |  2009  |  2008  |  Older

 

CURE For questions, please contact Julie Milder at the CURE office, 312.255.1801, or email julie@cureepilepsy.org.
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