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 Board, the Lay Review Council, and the scientific peer reviewers who generously volunteer their time to CURE.


2013 Research Awards

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

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 Julie's Hope Award

Paz/Huguenard

John Huguenard, PhD and Jeanne Paz, PhD
Stanford University

“Closed-loop control of injury-induced and genetic seizures using temporally precise cell-type-specific optogenetic manipulation”

Epilepsy is a common neurological disorder and a major source of disability, with a third of all epilepsies unresponsive to existing treatments. To develop new and effective treatments, it is critical to identify seizure control points in the brain - regions, cells and circuits. We recently developed an approach to deliver light to the brain to control the activity of specific cell types, which specifically blocked seizures without affecting normal brain activities. In this proposal, we will develop novel optogenetic tools to determine causal links between the activity of specific cell types and various seizure types in behaving rodents.



Naegele

Janice Naegele, PhD
Wesleyan University

GABAergic Interneuron Transplantation for Circuit Repair and Seizure Suppression in Temporal Lobe Epilepsy

This work will enable us to address an important gap in moving stem cell therapies from the bench to the clinic. Our investigations in adult mice with acquired temporal lobe epilepsy examine whether transplants of a major inhibitory cell in the brain, the GABAergic interneuron, can suppress seizures by repairing dysfunctional neural circuits in the hippocampus. Following transplantation of stem cell-derived GABAergic interneurons into the dentate gyrus, we will use optogenetics to study whether the transplanted cells suppress spontaneous seizures and prevent axonal sprouting by making strong inhibitory synapses onto newborn hyperexcitable granule neurons.





Prevention of Acquired Epilepsies Awards
Multiple-year grants (up to 3 years) to a maximum of $250,000 in support of research relevant to the prevention and treatment of acquired (post-insult) epilepsies

CURE grant award Brighter Future Award

Boison

Detlev Boison, PhD
Legacy Emanuel Hospital and Health Center

Prevention of Acquired Epilepsy Through an Epigenetic Intervention

New findings suggest that chemical changes introduced into the DNA of nerve cells, such as increased DNA-methylation, play a fundamental role in supporting those processes that lead to the development of epilepsy. Once those chemical alterations are established, they contribute to the maintenance and worsening of epilepsy. This grant is based on our discovery that adenosine – an endogenous anticonvulsant of the brain – also reduces DNA-methylation, and thereby has the potential to reverse DNA modifications in the epileptic brain. Using a mouse model of acquired epilepsy we will establish a new treatment paradigm to make therapeutic use of a transient dose of adenosine with the goal to prevent the development of epilepsy long-term.



Russek-Kayal

Shelley Russek, PhD & Amy Brooks-Kayal, MD
University of Colorado Denver & Boston University School of Medicine

“Development of Novel JAK/STAT Inhibitors for Disease Modification in Epilepsy”

Approximately 65 million people worldwide have epilepsy. Although certain brain injuries are known to predispose to epilepsy, there are no treatments that reduce this risk. We have found that an important cellular signaling pathway, the JAK/STAT pathway, is activated after brain injuries that lead to epilepsy, and that inhibiting this activation reduces subsequent seizure frequency in an animal model. The proposed studies will examine novel JAK/STAT inhibitors with the ultimate goal of identifying those with optimal chemical properties that obtain high brain concentrations, effectively inhibit JAK/STAT activation after injury, have low toxicity and are most efficacious in reducing or preventing seizures and/or cognitive co-morbidities in an animal model of acquired epilepsy. We expect to identify lead JAK/STAT inhibitors that can be advanced towards clinical testing to prevent or inhibit development of acquired epilepsy following brain injury.



D'Ambrosio

Raimondo D’Ambrosio, PhD
University of Washington

Prevention of Posttraumatic Epilepsy with FDA-Approved Anti-Inflammatory Drugs

The mechanisms that lead to the onset of epilepsy after head injury in humans are not known, but mounting evidence points to inflammation as a major contributor. We recently discovered that mild cooling of the injured brain, a treatment that dampens inflammation, potently prevents epileptic seizures after a realistic contusive head injury in the rat. There are numerous FDA-approved anti-inflammatory drugs which target a wide range of inflammatory mechanisms that, alone or in combination, could reproduce the potent antiepileptogenic effect of mild cooling. These drugs are safe and have been approved for various conditions, and could quickly enter clinical trials for the prevention of posttraumatic epilepsy, but no data are yet available to determine whether they are antiepileptogenic after head injury. We will test these drugs in formal blind and randomized studies to determine their antiepileptogenic potential and route them to phase III clinical trials.





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 2013 Christopher Donalty and Kyle Coggins Memorial
Buchanan

Gordon Buchanan, MD, PhD
Yale University

Role of Vigilance State and Circadian Phase in Seizure-Related Death

Sudden unexpected death in epilepsy (SUDEP) most commonly occurs at night, but why this happens is unknown. We hypothesize that this may be due to sleep state-dependent and/or circadian (time-of-day) variation in the respiratory and cardiac consequences of seizures. We further postulate that impaired functioning of the brain signaling molecule serotonin may be involved. To test this, we will employ a genetic mouse model of serotonin depletion to evaluate the effects of seizures which occur during different sleep-wake states and circadian times on breathing, heart control, and mortality. Understanding factors causing SUDEP to occur at night may lend insights regarding why it occurs at all, and ultimately lead to measures to prevent it.



CURE grant award Team S4 Award
Paterson

David Paterson, PhD
Boston Children’s Hospital

“Searching for Common Gene Variants in Sudden Death in Childhood with Febrile Seizures, SIDS and SUDEP”

Sudden unexplained death in childhood associated with febrile seizures (SUDC-FS) is the sudden unexplained death of a child that has a personal and family history of fever-related (febrile) seizures. These children have many features in common with individuals dying of SUDEP and SIDS, including sleep-related death and discovery in the prone position. We believe that these diseases have similar causes including gene mutations that cause seizures. There is a clear pattern of genetic inheritance in some SUDC-FS families. Genetic analysis of these families, as proposed in this study, provides an excellent opportunity to identify the genes responsible for SUDC-FS and therefore also SUDEP and SIDS. This study has the potential, therefore, to uncover novel information that could be used to diagnose and treat all individuals at risk from sudden unexpected death associated with seizure.



Tolner

Else Tolner, PhD and Arn van den Maagdenberg, PhD
Leiden University Medical Center (LUMC), the Netherlands

“Excessive Neuronal Inhibition Changes Physiological Functions and Increases SUDEP Risk”

Risk factors and mechanisms for SUDEP are largely unknown. Our research will test the hypothesis that suppression of brain activity after a seizure reflects increased neuronal inhibition and is linked to fatal outcome. We will use transgenic migraine mouse models carrying human pathogenic Cacna1a gene mutations, that exhibit various neurological disease features including fatal seizures. We hypothesize that these seizures are explained by the known enhanced level of neuronal excitation in our mice and excessive neuronal inhibition. By experimentally modulating the misbalance between excitatory and inhibitory neuronal activity, e.g. using drugs that affect adenosinergic inhibition, we expect to aggravate or ameliorate the SUDEP phenotype in our mice. Thus we hope to provide a mechanistic understanding of SUDEP pathophysiology and development of diagnostic tools for identifying susceptible individuals.





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

CURE grant award The Rock the Block for Pediatric Epilepsy Research Award
Coper

Edward Cooper, MD, PhD
Baylor College of Medicine

“Targeted molecular therapy for KCNQ2-associated severe pediatric epilepsy”

Potassium channels are part of the brain’s molecular machinery for electrical signaling. They generally provide a restraining function, and their loss can lead to excessive nerve activity and epilepsy. Mutations in the potassium channel gene KCNQ2 cause forms of epilepsy that begin within days after birth. The severity of KCNQ2-associated epilepsy varies from very mild to severe. In one form, KCNQ2-associated epilepsy is followed by profound, lifelong, developmental delay (epileptic encephalopathy). We will develop methods for augmenting KCNQ2 activity in individuals bearing such severe disease-causing mutations, using a combination of cell-based approaches and animal models.



CURE grant award The Vogelstein Pediatric Epilepsy Award
Simeone

Timothy Simeone, PhD
Creighton University

The Critical Role of PPARgamma in Ketogenic Diet Efficacy

The Ketogenic Diet (KD) is an effective broad-spectrum therapy for epilepsy that is primarily used for medically refractory pediatric patients. Elucidating the critical mediator(s) of KD efficacy will further our understanding of the basic mechanisms of epilepsy and open new avenues of drug discovery. To this end, our recent findings implicate a regulator of gene expression called PPARgamma as a mediator of KD anti-seizure efficacy. Our proposed studies will test investigational drugs, determine relevant functional mechanisms and explore possible strategies of reducing the stringency of the KD, thereby bringing us closer to the ultimate goals of No Seizures/No Side Effects.





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 The Rock the Block for Pediatric Epilepsy Research Award
Hardwick

J. Marie Hardwick, PhD
Johns Hopkins University

“Autophagy defect in epilepsy”

New information about the specific causes of epilepsy is paramount to make progress against these devastating disorders. Using yeast genetics as a tool to find new regulators of cell death, we identified an uncharacterized yeast gene with homology to a human gene mutated in children with a form of intractable epilepsy. However, there is no information about the function of this human gene. By generating an animal model of this new epilepsy syndrome, we seek to translate our unique information from yeast to explain a new cause of epilepsy and to provide a model for testing new therapies.



Heinrich
Depaulis

Christophe Heinrich, PhD & Antoine Depaulis, PhD
Grenoble Institute of Neuroscience, INSERM

“Conversion of reactive glia into neurons in Mesial Temporal Lobe Epilepsy: a new way to generate GABAergic interneurons and reduce seizure activity?”

Mesio-Temporal Lobe Epilepsy (MTLE), the most common form of intractable epilepsies, is associated with loss of inhibitory neurons and proliferation of glial cells, both of which have been suggested to play a critical role in epilepsy development. Therefore a procedure to re-introduce new inhibitory neurons and limit glial proliferation within hippocampal networks represents an innovative strategy to reduce seizures. Reprogramming one cell type into another represents a novel strategy for brain repair. We previously showed that glial cells from the cortex can be reprogrammed into inhibitory neurons. Our project aims at reducing seizures in a MTLE mouse model through forced reprogramming of hippocampal glial cells into functional inhibitory neurons. If successful, glia-to-neuron conversion could prevent epilepsy development and/or attenuate seizures in the chronic phase of the disease. Thus this proof-of-concept approach could create a new avenue for innovative anti-epileptogenic strategies for MTLE patients.



Hermann
Matti Sillanpaa

Bruce Hermann, PhD
University of Wisconsin, Madison

Matti Sillanpaa, MD, PhD
University of Turku, Finland

“Brain Aging in Persons with Childhood Onset Epilepsy: A Population Based Investigation”

The purpose of this project is to characterize patterns of cognitive and brain aging in persons with childhood onset epilepsy. This issue is addressed in a unique population-based cohort from Finland consisting of healthy individuals and persons with childhood onset epilepsies followed since childhood/adolescence, now 45-62 years old. For this project the cohort is returning for assessment of memory and other cognitive abilities, sophisticated neuroimaging to examine brain structure and function, EEG, and detailed interview. The results will provide unprecedented insights into the very long term cognitive and brain health of persons with childhood epilepsies.



McCown

Thomas McCown, PhD
University of North Carolina, Chapel Hill

“An Essential Element for Novel, Astrocyte Focused Epilepsy Therapies: the Creation of a Chimeric, Astrocyte Selective Adeno-associated Virus Vector”

Seizures impair the function of several types of cells in the brain. Impairment of the astrocyte cells leads to an environment that favors further seizure activity. To date, no means exist to efficiently express genes in astrocytes that could restore normal cellular function. Therefore, using previously successful advanced techniques, we propose to create novel virus vectors that selectively target astrocytes. A successful outcome has far reaching implications for epilepsy therapy. With an established astrocyte selective virus vector, the potential exists to reverse the pro-seizure environment and subsequently prevent seizure activity. Importantly, this therapeutic approach would not directly alter function of the neurons, which is the primary cause of negative side effects.





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

Jones

Nigel Jones, PhD
University of Melbourne

“DNA methylation in epilepsy”

In cases of acquired epilepsy, such as those resulting from head injury, the levels of many different proteins within the brain change dramatically. Many of these changes contribute to the generation of epilepsy. This experimental research will investigate an overarching molecular mechanism which mediates these wide-spread changes in protein expression following brain injury, and will determine whether blocking this mechanism can prevent the negative impact these protein changes exert on the brain. It is hoped that by providing a pharmacological intervention immediately following head injury in patients, we can prevent the changes in protein expression within the brain from occurring, and ultimately stop the development of the epilepsy following the injury.



Berdichevsky

Yevgeny Berdichevsky, PhD
Lehigh University

“IGF-1 signaling in posttraumatic epileptogenesis”

Traumatic brain injury activates complex molecular signals in surviving neurons. Some of these signals are thought to cause posttraumatic epilepsy. This project relies on high-throughput bioengineering methods to identify the precise roles that these signaling molecules play in the development of epilepsy. To further CURE’s mission of achieving No Seizures/No Side Effects, we will: 1), design and optimize antiepileptic treatments that inhibit multiple signaling nodes at appropriate times, and 2), use high-throughput methods to discover other signaling pathways that are involved in epileptogenesis and that may be effective drug targets. Our goal is to find a combination of signaling pathways that could be inhibited for complete prevention of epilepsy with minimal side effects.



Wolf

John Wolf, PhD
University of Pennsylvania

“Network and Axonal Mechanisms Underlying the Transition to Post-Traumatic Epilepsy Following Repetitive Mild Traumatic Brain Injury (Concussion)”

There is an increased risk of epilepsy onset following a mild traumatic brain injury (concussion). However, the mechanisms underlying this process are unknown. We are therefore evaluating circuitry changes over time after injury in the hippocampus, a vulnerable brain area in both epilepsy and trauma. We hope to understand how these alterations lead to epileptic activity after injury. We are also testing a promising intervention that blocks inflammatory processes contributing to circuit dysfunction in the hippocampus. Establishing a mechanistic link between repetitive concussions and epilepsy would be a powerful way to reduce the number of new epilepsy cases.



Taniguchi

Hiroki Taniguchi, PhD
Max Planck Florida

“Towards a chandelier cell-based cure for epilepsy”

Development of novel strategies to more efficiently and safely cure epilepsy is urgent for both clinical and basic neuroscientists. Chandelier cells are the most powerful inhibitory neurons, and they can be useful for a cell transplantation therapy to reduce seizures. First, we will test if transplantation of chandelier cells into an animal model of epilepsy can reverse the seizure phenotype. Second, we will identify genetic programs that specifically lead to the development of chandelier cells. Our research will provide key insight into future clinical applications of cell transplantation.





 

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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