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

Grant recipients were selected with the invaluable assistance of the CURE Scientific Advisory Board and the CURE Research Review Board.

2013  |  2012  |  2011  |  2010  |  2009  |  2008  |  Older

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

2012 Research Awards

Challenge Awards
Two- to three-year grants up to $250,000 for established investigators

CURE grant award The CJM Foundation Award
Crino

Peter Crino, MD, PhD
Temple University

“A Novel Transposon Causes Focal Cortical Dysplasia”

Focal malformations of cortical development (FMCD) are a common cause of intractable pediatric epilepsy. Some FMCD arise from gene mutations whereas others result from unknown causes. Many FMCD subtypes are associated with abnormalities in mammalian target of rapamycin (mTOR) signaling. We have recently found that the human papilloma virus 16 (HPV16) oncoprotein E6, a known activator of mTOR, is expressed in focal cortical dysplasia, a type of FMCD. These results suggest an association between HPV16 E6 and FMCD and demonstrate HPV16 E6 for the first time in the human brain. We will investigate other forms of FMCD to determine whether HPV or related viral oncoproteins can be detected. If our data is correct, the future for patients with FMCD may include targeted therapy to cure HPV16 infection that could lead to truly new and successful treatment strategies with improved efficacy (“no seizures”) and diminished morbidity (“no side effects”). Indeed, defining the molecular pathogenesis of FMCD as an infectious agent would open a cascade of ideas, experiments, and approaches that may have direct patient benefit and alter how we design therapies for intractable epilepsy.



CURE grant award The Heldman Family/CURE Award
Fujinami

Robert Fujinami, PhD
University of Utah

“New Treatments for Epilepsy that Regulate Complement Activity”

Virus infections causing inflammation in the brain frequently induce seizures. We have developed a new model where virus infection of mice results in acute seizures. About a month after infection the virus is cleared from all tissues. Interestingly, after a variable period where no seizures are observed, animals develop recurrent spontaneous seizures (epilepsy). This is the first infection driven model of epilepsy. It is becoming clear that inflammation in the brain contributes to seizures. A participant in inflammation in the brain is the complement system. This system is enhanced in the brains of individuals with epilepsy. We propose to test the hypothesis that virus infection activates the complement system in the brain that in turn increases inflammation which ultimately contributes to the development of seizures. Novel therapies that inhibit complement activation will be tested to ascertain their ability to block the initiation of seizures and/or treat epilepsy once it has started.



Multidisciplinary Award
Two- year grants up to $350,000 in support of collaborative research

CURE grant award The Brighter Future Award
Schiff/Read

Steven Schiff, MD, PhD, Andrew Read, PhD, Bruce Gluckman, PhD, Patrick Drew, PhD, Jose Antonio Stoute, MD
Pennsylvania State University

“A Murine Model for Preventing Postmalarial Epilepsy”

The rates of childhood epilepsy in malaria prone regions of the developing world are substantially higher than in industrialized countries. Although epilepsy is well described as a consequence of cerebral malaria, we do not understand how to prevent these large numbers of people, mostly children, from developing epilepsy after cerebral malaria. This project represents a multidisciplinary effort of an epilepsy specialist, a malaria biologist, an experimental physicist, a malaria clinician, and an optical imaging expert towards exploring several likely mechanisms at preventing post-malarial epilepsy. Our translational approach focuses on fusing fundamental biology and clinical principles to help guide future human clinical trials.



CURE grant award The Dravet Syndrome Foundation Award
Kang

Jingqiong “Katty” Kang, MD, PhD
Vanderbilt University

“Probing synaptic changes in a novel mouse model of severe epilepsy with nanoparticle-enabled 3D super-resolution imaging”

Normal brain function requires a precise balance between excitation and inhibition. Too much excitation or too little inhibition can result in seizures or epilepsy. A protein family called GABAA receptors (GABAAR) mediates brain inhibition. A single mutation in the genes of the protein family can cause different kinds of epilepsy. We have made a mouse model carrying a mutation in a gene that causes a severe form of epilepsy known as Dravet Syndrome. The mice carrying this mutation had seizures and other neurodevelopmental abnormalities. This provides us a very useful window to understand the pathophysiology of epilepsy. We propose to use photoluminescent nanoparticles called quantum dots to perform 3D super-resolution tracking of the dynamic behaviors of this protein family in live neurons in the mutation-carrying mice. In combination with multiple molecular, biochemical, electrophysiological and behavioral approaches, we will determine the changes of GABAAR membrane dynamics, synapse formation, connectivity, plasticity as well as synaptic transmission of inhibitory neuronal circuit. We hope this study will bring us a step closer to finding a cure for epilepsy.



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 Madison Friends of CURE Award
Haydon

Philip Haydon, PhD
Tufts University

“Astrocyte receptors as a therapeutic target for treating epilepsy”

While much of the past focus on the development of new therapies for epilepsy has concerned important roles played by nerve cells, it is also thought that glia, electrically silent cells that make up half of the brain, are likely to be involved in this brain disorder. However, their roles are unknown. Using recent technical innovations we will determine how a type of glial cell, called the astrocyte, regulates the development of epilepsy with the long term objective of targeting astrocytes to prevent epilepsy.



Jones/Gonzalez

Stephen Jones, MD, PhD
Cleveland Clinic

Jorge Gonzalez-Martinez, MD, PhD
Cleveland Clinic

“Localizing epileptic foci by simultaneous intracranial stimulation and fMRI”

A major form of epilepsy – focal epilepsy – is highly curable by surgical removal, if the correct portion of the brain can be identified. We propose a novel method to better identify this portion of the brain by using a unique combination of two cutting edge technologies: intracranial electrode implantation with “functional” MRI, within the operative environment. Never performed before, we anticipate this method will better identify the regions of the brain responsible for causing focal epilepsy, add a new technique available to our doctors, and improve surgical outcomes and benefit thousands of patients.



Moss

Stephen Moss, PhD
Tufts University

“Restoring the function of the K+-Cl- cotransporter to limit pharmacoresistant seizures”

Drug resistant seizures are common in epilepsy, and these events directly contribute to premature death and reduce the quality of life for a significant proportion of patients. We believe these so-called “pharmacoresistant” seizures result from a failure in neuronal inhibition, due in part to abnormal intracellular accumulation of chloride. Here we will test the ability of recently identified pharmacological agents that are able to normalize intracellular chloride levels, to terminate pharmacoresistant seizures in rodents. Collectively these studies may lead to the development of novel therapies to treat drug resistant seizures, with minimal side effects.



Hsu/Worrell

David Hsu, MD, PhD
University of Wisconsin Madison

Gregory Worrell, MD, PhD
Mayo Clinic

“Time-resolved wide-band analysis of EEG using the damped-oscillator oscillator detector (DOOD)”

Brief, high frequency EEG oscillations appear to mark areas of brain that are important in generating seizures. However, it is very time-consuming to identify these oscillations visually. Drs. Hsu and Worrell have developed a computer algorithm to detect these oscillations automatically. Their method is similar to how the human ear picks out sound tones, i.e. oscillations, with high time and frequency resolution. In a collaboration between the University of Wisconsin and Mayo Clinic, Drs. Hsu and Worrell will develop this algorithm for use in epilepsy surgery. If successful, people who undergo epilepsy surgery for refractory epilepsy will have a better chance of becoming seizure-free.



Taking Flight Awards
One-year grants up to $100,000 in support of young investigators

Quilichini

Pascale Quilichini, PhD
INSERM, France

“Local dynamics and dialog among hippocampo-entorhinal networks in a model of temporal lobe epilepsy in vivo”

Temporal lobe epilepsy is the most common form of epilepsy in adults and many remain resistant to drug treatment. Besides seizures, patients often have severe cognitive deficits, as well. Our assumption is that the deficient cognitive functions and seizure generation emerge from an alteration of the communication between temporal neuronal networks. In order to help CURE achieve the goal of "no seizures and no side effects", we seek to understand these complex mechanisms using an in vivo approach. Our project aims to decipher the communication between neuronal networks in an animal model of temporal lobe epilepsy. We will use high-density electrodes to read the activity of large neuronal networks in an effort to determine whether the alterations detected might contribute to seizures and/or to cognitive deficits.



Lim

Kuei-Cheng Lim, MD, PhD
University of Pennsylvania

“Manipulation of mTOR signaling in focal cortical dysplasia related epilepsy”

A significant portion of patients with medically refractory epilepsy are found to have focal cortical dysplasia, an area of brain tissue with abnormally developed and oriented neurons and glial cells. Tuberous sclerosis complex (TSC) is a well-known inherited cause of epilepsy with cortical dysplasia due to a mutation in one of two genes, Tsc1 and Tsc2. TSC1 and TSC2 are regulators of the mTOR signaling pathway, which is a central cellular signaling pathway that regulates growth, cellular proliferation, and migration. Dr. Lim is studying the neuronal subtypes, cortical development, and electrographic seizures caused by excessive mTOR activity by disrupting Tsc1 or Tsc2 in mice during the prenatal period. Using this animal model, Dr. Lim will define cellular targets of the mTOR signaling pathway to aim to prevent the abnormal development of cortical dysplasia and thus seizures during the fetal period.



Feng

Huajun Feng, MD, PhD
Massachusetts General Hospital & Harvard Medical School

“Role of Central 5-HT Transmission in Respiratory Arrest Induced by Seizures”

Seizure-induced suppression of breathing (apnea) causes sudden unexpected death in epilepsy (SUDEP). Post-seizure apnea in an animal model of SUDEP is reduced after injection of a drug that enhances the level of a nerve cell signaling molecule called serotonin (5-HT), suggesting that defective 5-HT signaling may contribute to SUDEP. However, there is no current information about where in the brain 5-HT supposedly acts to sustain breathing after seizures. The goal of this project is to use state-of-the-art neuroscience methods to explore which brain structure(s) are involved in seizure-evoked apnea and the role of several 5-HT receptors in this phenomenon. If successful, our findings may lead to new treatments that prolong the lives of epileptic patients.



Viventi

Jonathan Viventi, PhD
Polytechnic Institute of New York University

“Suppressing Seizure Initiating Patterns with High-Resolution Active Electrode Arrays”

Dr. Viventi's research applies innovations in flexible electronics to create new technology for interfacing with the brain at over 400 times higher spatial resolution than today’s clinical devices. With funding from CURE, his group will develop this technology to map abnormal brain activity over broad regions and to electrically stimulate these regions to abort seizures with exquisite precision. This technology opens an entirely new window into understanding brain function, and new methods for localizing and treating seizure generating brain regions in patients with epilepsy.



Huang

Yangzhong Huang, MD, PhD
Duke University Medical Center

“Targeting of Src Family Kinases for Treatment of Mesial Temporal Lobe Epilepsy”

Temporal lobe epilepsy is a major public health problem because it is both common and frequently resistant to treatment. There is no effective prevention. Src family kinases (SFKs) are a family of signaling molecules that have been implicated in diverse physiological and pathological conditions. Experimental evidence has led to the hypothesis that SFKs promote epileptogenesis in vivo. In this project, I will use biochemistry and mouse genetics to investigate the role of SFKs in epileptogenesis. These findings will hopefully elucidate some of the molecular signaling mechanisms underlying epileptogenesis and identify novel molecular targets for prevention of temporal lobe epilepsy.



Sebe

Joy Sebe, PhD
University of California, San Francisco

“Determining the role of GABA activity in interneuron development: toward developing a cell therapy for epilepsy”

Dr. Sebe has been working with a research team at the University of California, San Francisco to develop a cell therapy for epilepsy. Previously, they have demonstrated that inhibitory neural progenitor cells transplanted into newborn epileptic mice dramatically suppress seizures as the animals mature. To increase the speed at which these progenitor cells incorporate into the epileptic brain and to potentially boost their therapeutic efficacy, Dr. Sebe is looking for molecular cues and drugs that promote cell development. To test a large number of compounds in an intact developing animal, she is turning to transgenic zebrafish in which the inhibitory neural progenitor cells fluoresce and can be easily tracked. The Taking Flight Award will allow Dr. Sebe to begin what will become an independent research program in which she will examine the cues that guide neuron development and optimize new therapies for epilepsy.



SUDEP Awards
One-year grants up to $100,000 in support of SUDEP research

CURE grant award The CURE & HOPE4SUDEP Award in honor of Cameron Benninghoven
Glasscock

Edward Glasscock, PhD
Louisiana State University Health Sciences Center

“Pharmacological reversal of cardiorespiratory deficiency in the Kcna1-null model of SUDEP”

The two leading mechanisms for SUDEP are seizure-related cardiac and respiratory dysfunction. This research tests the ability of two clinically available drugs, flupirtine and fluoxetine, to prevent death in a well-characterized model of human SUDEP, the Kcna1 potassium channel knockout mouse, which exhibits severe seizures, brain-driven heart dysfunction, and premature death. Flupirtine belongs to a class of drugs called KCNQ openers, which we predict will protect against SUDEP by normalizing the interplay between brain and heart. Fluoxetine (better known as Prozac) prevents the brain’s reuptake of the neurotransmitter serotonin, which we predict will protect against seizure-associated respiratory arrest and SUDEP.



CURE grant award The Rock the Block for Pediatric Epilepsy Research Award
Semsarian/Scheffer

Chris Semsarian, PhD / Ingrid Scheffer, MD
University of Sydney/University of Melbourne

“Neuro-Cardiac Genetic Basis of Sudden Unexpected Death in Epilepsy (SUDEP)”

Sudden unexpected death in epilepsy (SUDEP) is the most common epilepsy-related cause of death. SUDEP is characterised by a sudden, unexpected, and non-traumatic death in a patient with epilepsy, where the post-mortem does not reveal a cause of death. The underlying cause of SUDEP remains unknown. There is emerging evidence that changes in our DNA (genes) found in the heart and brain, may be a key underlying cause of SUDEP. The proposed genetic study will be of benefit to surviving family members, both in terms of earlier diagnosis, closer clinical surveillance and initiation of early therapies to prevent the occurrence of SUDEP.



Sisodiya

Sanjay Sisodiya, PhD
University College London

Samden Lhatoo, MD
Case Western Reserve University

Maria Thom, MD
University College London

Jane Hanna
Epilepsy Bereaved

“The Brain in Sudden Unexpected Death in Epilepsy (SUDEP) - New Insights from Pathology”

Successful, rational, prevention strategies ultimately come from better understanding of the causes and mechanisms of disease. By definition, SUDEP is unexplained: we do not know why it happens, which currently makes prevention very difficult. SUDEP occurs when the brain is affected by epilepsy, and it may relate to individual seizures. We possess a unique archive of brain tissue from people who died of SUDEP and others who did not. We plan to examine and compare these brains in detail, and determine whether there are differences that can give us clues to the cause of SUDEP.



CURE grant award The 2012 Christopher Donalty & Kyle Coggins Memorial Award
Pitt

Geoffrey Pitt, MD, PhD
Duke University

“Development of a Mouse Model for SUDEP”

Causes for SUDEP are unknown. Although heart arrhythmias are suspected, this has not been definitively demonstrated. Progress on determining causes, and thereby developing means to identify at-risk patients or preventing occurrence, has been impeded by the lack of animal models. We propose a novel hypothesis that mutations in broadly expressed ion channel modulators could affect brain channels (causing seizures) and also alter cardiac channels, thereby increasing susceptibility to life-threatening arrhythmias. We propose to test this hypothesis with new animal models, leading to the rational discovery of SUDEP candidate genes and development of diagnostic tools for identifying susceptible individuals.

 

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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