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

CURE grant recipients by year:
2016  |  2015  |  2014  |  2013  |  2012  |  2011  |  2010  |  2009  |  2008  |  Older


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

Henshall

David Henshall, PhD
Royal College of Surgeons in Ireland

Teresa Maloney, PhD
University of Oxford

“LGI1 autoantibodies as a cause and therapeutic target for seizure control”

The immune system occasionally launches a strike on one of its own proteins, generating self(auto)antibodies. Autoantibodies against brain proteins have recently been discovered in patients with difficult-to-treat epilepsies of unknown cause, including some that bind a secreted protein involved in communication called LGI1. This project will test models of autoantibody transfer to determine if these LGI1 antibodies are sufficient to cause seizures and interfere with brain functions such as memory. We will also look at the molecular changes that occur after exposure to the autoantibodies to understand the mechanism by which they promote seizures.



Vezzani

Annamaria Vezzani, PhD
Istituto di Ricerche Farmacologiche Mario Negri (IFRMN) - Milan, Italy

“HMGB1 as a target and a mechanistic biomarker of epileptogenesis”

The next generation of therapies for epilepsy needs to target the mechanisms intimately involved in making the brain susceptible to spontaneous seizures. Such drugs could be used to prevent the onset of epilepsy in susceptible individuals or favourably modify its course after the disease onset. A major area of interest in epilepsy research relates to inflammation. We have shown that one specific molecule, which is known by the acronym HMGB1, is closely involved in seizures, and its presence in epileptic brain tissue is an indicator of neuroinflammation. It is produced and released by injured brain cells and can be measured in the bloodstream. The project goals are to use experimental models to prove the HMGB1 involvement in epilepsy development and its comorbidities, the utility of blood HMGB1 for predicting disease development and the therapeutic response to treatment, and the anti-epileptogenic effects of a new combination of medically used drugs targeting HMGB1.




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 Team S4 Award
Natalia De Marco Garcia

Natalia De Marco Garcia, PhD
Cornell University

“Regulation of cortical interneuron migration and epilepsy”

Many neurological illnesses including a subset of pediatric epilepsies are thought to arise during the development of the nervous system. Increasing experimental evidence points towards imbalances between the excitatory and inhibitory circuits in the brain as a prominent component in the generation of epilepsy. The goal of this proposal is to assess how environmental perturbations during a critical period of development affect inhibitory connections and lead to abnormal brain activity. We will focus our studies in a subset of inhibitory neurons since our previous work indicates that these neurons are exquisitely sensitive to environmental stress in newborns. We hope that our studies will inspire therapies to correct aberrant brain formation in epilepsy.



King

Glenn King, PhD
The University of Queensland, Australia

Steven Petrou, PhD
Florey Institute of Neuroscience and Mental Health

“A novel therapeutic intervention of Dravet syndrome”

Dravet syndrome (DS) is a catastrophic pediatric epilepsy characterized by severe drug-resistant seizures, intellectual disability, autistic traits, movement disorders and increased risk of sudden death. Most DS cases are due to mutations in an ion channel known as Nav1.1 (gene named SCN1A) that is found in neurons responsible for calming brain activity. In DS, the aberrant function of these neurons leads to increased brain excitability and seizures. We have identified compounds that enhance Nav1.1 function in order to control seizures, and we aim to develop these molecules as therapies. This project has the potential to revolutionize the treatment of DS and related epilepsies.



Ho Lee

Jeong Ho Lee, MD, PhD
Korea Advanced Institute of Science and Technology

“Molecular Genetic Decoding of Brain Somatic Mutations in Intractable Pediatric Epilepsies”

Genetic abnormalities in small areas of the brain can lead to disruption of the entire brain by interfering with normal neuronal signaling. Focal epilepsies in children are one example of this and genetic mutations arising in specific brain regions can lead to abnormally synchronized electrical discharges and seizures. In this project, we will systematically uncover mutations occurring in the brain of children with intractable epilepsies who have undergone epilepsy surgery. The identification of brain-only genetic mutations will not only reveal the cause of the epilepsy, but will also provide information on biomarkers and medically actionable targets, which are important as we seek to treat these childhood drug-resistant epilepsies.




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

McKhann

Guy McKhann, MD
Columbia University Medical Center

“Targeting the mTOR pathway in glioma-associated epilepsy in mice and humans”

Epilepsy is the most common presenting symptom of an adult glioma. A multidisciplinary team will study a mouse glioma model that closely parallels the human disease to determine when seizures arise, and we will see if we can prevent or treat seizures by blocking the mTOR pathway with an oral drug that is FDA approved for human use. We will also use EEG brain recordings before and during human surgery to determine the “seizure prone” electrically abnormal areas on the margins of tumors. Finally, we will establish a pre-clinical study in glioma patients in which we give patients an mTOR inhibitor the day prior to surgery and then study the resected tumor tissue to see whether this treatment decreases mTOR pathway activation and electrical excitability in the cells around the tumors.



Newell-Rogers

Karen Newell-Rogers, PhD
Lee Shapiro, PhD

Texas A&M University System Health Science Center

“The Contributions of CD74 to Acquired Epilepsy”

Epilepsy occurs in 15 to 20% of traumatic brain injuries. Who acquires post-traumatic epilepsy (PTE), and why, is unknown. While injury type and severity influence who gets epilepsy, similar injuries can cause PTE in one person, but not in another. The answer to why similar injuries can have such different outcomes may lie in the differences between individuals’ immune responses. TBI causes inflammation and can elicit an immune response. We have also discovered that targeting components of the immune response can suppress inflammation after TBI. The purpose of this proposal is to determine if we can prevent PTE by selectively targeting a damaging immune response after TBI.



Shafi

Mouhsin Shafi, MD, PhD
Alvaro Pascual-Leone, PhD
Igor Koralnik, MD

Beth Israel Deaconess Medical Center

“Measuring and Modifying Cortical Hyperexcitability in Patients at High Risk for Acquired Epilepsy”

Epilepsy is a common complication of many acquired brain injuries such as stroke, brain infections, and traumatic brain injury. However, any one person’s likelihood of acquiring epilepsy after a brain injury is usually low, and there are no tests to help identify which individuals are particularly likely to develop seizures. As a result, research to help prevent acquired epilepsy in patients has been difficult. Furthermore, there are no approved treatments that directly affect the brain processes involved in the development of epilepsy. We will utilize a noninvasive brain stimulation technique, Transcranial Magnetic Stimulation (TMS), in combination with electroencephalography (EEG) to evaluate brain excitability, and thereby the risk of developing epilepsy, in patients with an acquired brain infection called Progressive Multifocal Leukoencephalopathy (PML). We will then assess whether multiple sessions of repetitive TMS can decrease brain excitability in high-risk patients, and thus potentially prevent the development of seizures.




SUDEP (Sudden Unexpected Death in Epilepsy) Awards
Two-year grants up to $250,000 in support of innovative studies that will provide new directions for SUDEP research.

Glasscock

Edward Glasscock, PhD
LSU Health Sciences Center in Shreveport

Leon Iasemidis, PhD
Louisiana Tech University

“Employment of in vivo biosignal dynamics as biomarkers of SUDEP”

This research seeks to identify novel biological signal patterns that can be used as reliable markers to predict SUDEP risk. We will identify these biosignal patterns by performing innovative mathematical analyses of simultaneous recordings of brain, heart, and lung activity in a two gene model of human SUDEP (Scn2a, Kcna1 double mutant mouse). Currently, utilization of biosignal analyses for the study of SUDEP is very limited and mainly restricted to individual EEG analysis. The envisioned project has the potential to widen this field by applying bioengineering analytical principles to identify interactions and associations between biosignals that can be used to predict SUDEP risk.



Goldman

Alica Goldman, MD, PhD
Baylor College of Medicine

Tara Klassen, PhD
University of British Columbia

Torbjorn Tomson, MD, PhD
Karolinska Institutet

“Pilot in silico mortality risk attribution in SUDEP and sudden death in the young (SUDY) to inform precision molecular diagnostics of sudden death”

Sudden unexpected death in the young (SUDY) is the tragic mortality affecting otherwise healthy individuals. It includes sudden death in epilepsy (SUDEP), sudden infant death (SIDS), and sudden cardiac death (SCD) syndromes and there are overlapping candidate mechanisms that seem to converge on cardiac, respiratory or autonomic (cra) pathways in all of these. We will perform whole genome sequencing on DNA samples from patients that died of SUDEP, SCD, and SIDS to understand the genomic variation in cardiac, respiratory or autonomic pathways and we will use bioinformatic analyses to understand the point of overlap in these genetic networks. The results of this work will inform models for risk prediction in SUDEP and in SUDY overall.



Isom

Lori Isom, PhD
Jack Parent, MD

University of Michigan

“Patient-specific induced pluripotent stem cell cardiac myocytes as predictors of SUDEP risk”

Mutations in ion channel genes cause Dravet Syndrome (DS) and several other forms of severe childhood epilepsy. Many of these ion channels, which are critical for electrically excitable tissues, are present in the heart in addition to the brain. We propose that heart rhythm may be altered in genetic epilepsy and that heart abnormalities may contribute to SUDEP. We were the first to demonstrate altered cardiac excitability in mouse models of DS caused by SCN1A and SCN1B mutations. Our new results suggest that DS patient-derived heart cells generated from skin cells using the induced pluripotent stem cell (iPSC) method have altered beating rates and ionic currents and may be useful in predicting SUDEP risk. We will test the hypothesis that genetic epilepsy patients who are at greater risk of SUDEP will exhibit a higher beating rate and higher levels of sodium current in their iPSC-cardiac heart cells compared to people who do not have epilepsy. If so, then our work may lead to a diagnostic test for SUDEP risk.




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 Team S4 Award
Bordey

Angelique Bordey, PhD
Yale University

“Exosomes as carriers of circuit alterations in epilepsy”

This research aims at gaining novel insights into the biological processes that lead to cognitive deficits and psychiatric problems in children with epilepsy. More specifically, this work will examine whether the transfer of small vesicles (called exosomes) between abnormal brain cells leads to changes in the surrounding brain wiring. We will focus on abnormal “epileptic” neurons, like those found in focal cortical dysplasia and tuberous sclerosis complex, and will examine whether these cells alter the structure or electrical activity of healthy, neighboring neurons through the release of exosomes. If exosomes released from “epileptic” neurons do alter the function of healthy neurons, this would open up an entirely new field of epilepsy research.



CURE grant award Innovator Award in Honor of CURE365
Marchi

Nicola Marchi, PhD
CNRS Delegation Regionale Languedoc Roussillon, France

“Pericyte PDGFRB signaling during seizures: Characterization of a new mechanism of disease”

Seizures remain difficult to control in a significant percentage of patients. Increasing evidence indicates that epilepsy can be caused by vascular disease in the brain and that abnormal neuronal activity is linked to blood vessel dysfunction in the brain. Targeting the damaged brain vasculature could represent a therapeutic approach to end seizures. We propose that a key brain vasculature receptor called PDGFRb regulates the brain's blood flow response to seizures, and we will explore whether modulation of the receptor using specific medications can stop seizures.




CURE Award
One-year grants up to $50,000 in support of the exploration of a concept or theory that addresses an important problem relevant to epilepsy.

Rytting

Erik Rytting, PhD
Marxa Figueiredo, PhD

University of Texas, Galveston

“Targeted delivery of carbamazepine for improved antiepileptic drug therapy during pregnancy”

Because uncontrolled seizures during pregnancy can lead to serious consequences for both mother and child, pregnant women with epilepsy should continue their anti-seizure medication throughout pregnancy. However, prenatal exposure to such drugs is linked to increased risks for birth defects. The goal of this project is to develop nanoparticles that will accumulate in the brain to treat the epilepsy and thereby reduce the amount of medication crossing the placenta and affecting the baby’s development. If successful, this work will lay the foundation for preventing seizures in the mother while decreasing the risk of birth defects to the unborn child.




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.

Ahmed

Omar Ahmed, PhD
Brown University

“Autonomous seizure prevention using bioluminescence-driven optogenetics (BLOG)”

Seizures arise due to over-active subtypes of brain cells. Our goal is to prevent seizures by helping individual brain cells self-regulate their own activity, without the need for invasive electrodes, monitoring devices or implanted batteries. To do so, we create a modification of optogenetics, a tool that uses light to alter the activity of specific cells. By causing brain cells to emit their own light when they get over-active, we will let them control their own activity automatically, without the need for external light sources. We call this new technique bioluminescence-driven optogenetics, or BLOG. This powerful technique holds the promise to be a novel, non-invasive way to treat many different kinds of epilepsies.



Birnbaum

Ramon Birnbaum, PhD
Ben-Gurion University of the Negev, Israel

“Deciphering the gene regulatory networks in human inhibitory interneurons and their role in infantile spasms”

Epilepsy is a complex and heterogeneous disease which makes it difficult to precisely diagnose and provide an effective treatment. A major cause of epilepsy could be mutations in gene regulatory elements that instruct genes when, where and at what levels to turn on or off. Disruption of these elements in human inhibitory interneurons could be a cause for infantile spasms, an early-onset epilepsy. Here, we will identify and characterize gene regulatory elements of human inhibitory interneurons that could be associated with infantile spasms. This study will pave the way for screening epilepsy patients for mutations not only in genes but also in these regulatory elements, thus improving our ability to genetically diagnose epilepsy and hence provide more effective treatments.



Carvill

Gemma Carvill, PhD
University of Washington

“Epigenomic approaches to epilepsy”

Mutations in a number of genes have been shown to cause epileptic encephalopathy, one of the most severe types of epilepsy. Many of these genes control the expression of other genes i.e. they are responsible for switching certain genes ‘on’ or 'off' during the development and/or functioning of the brain. Here, we will use a new genome-editing technology to introduce mutations into two of these genes and create neuronal models of epilepsy. We will then study how mutations in these genes disrupt gene expression, and which pathways are affected. Identifying these pathways is the first step in finding new targets for therapeutics and understanding how genetic mutations cause epilepsy.



Goffin

Darren Goffin, PhD
The University of York, United Kingdom

“Genetic and optogenetic dissection of seizures in Rett Syndrome”

Rett syndrome (RTT) is a devastating neurological disorder that represents the second leading cause of intellectual disability in females. RTT patients suffer frequent and severe seizures that place a tremendous burden on patients and caregivers. Although models of RTT recapitulate many symptoms observed in patients, they exhibit few, if any, spontaneous seizures. Thus, the underlying cellular and circuit mechanisms leading to the manifestation of RTT-associated seizures remain unknown. We recently developed new models that exhibit robust RTT-associated behavioral and electrographic seizures. In this proposal, we will first dissect the specific cell types that mediate RTT-related seizures. Next, we will develop strategies to control seizure manifestation. These studies will provide new insights into the pathogenesis of seizures in RTT and may aid in the development of new strategies for their control.



Novarino

Gaia Novarino, PhD
Institute of Science and Technology, Austria

“Modeling epileptic encephalopathies in human brain organoids”

Early infantile epileptic encephalopathies (EIEEs) are a group of devastating disorders characterized by intractable seizures, global developmental delay and intellectual disability. EIEEs are highly genetic, meaning that often a genetic mutation is the basis of the disorder, however, in most of the cases the underlying mutation is very rare. Recent data suggest that distinct EIEEs may converge along specific molecular pathways. Can we identify these points of convergence? We aim to employ human “mini brains” to compare the effect of a large number of genetic mutations and identify points of intersection between distinct forms of EIEEs. The identification of these molecules will be the basis of future studies aiming to develop novel treatments.



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



 

CURE grant recipients by year:
2016  |  2015  |  2014  |  2013  |  2012  |  2011  |  2010  |  2009  |  2008  |  Older

 

CURE For questions, please contact Liz Higgins at the CURE office, 312.255.1801, or email liz@CUREepilepsy.org.
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