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

CURE Epilepsy Awards
Two-year grants up to $250,000 in support of scientific advances that have the potential to truly transform and save the lives of those affected by epilepsy.

Barth

Daniel Barth, PhD
University of Colorado – Boulder

“The Role of Neuro-inflammation in a Rat Model of Comorbid Epilepsy and Autism”

Thirty percent of children with epilepsy also have autism and vice versa. Dr. Barth’s group has recently discovered that suspected environmental risk factors for autism, such as maternal stress and certain common prenatal drugs, only when combined, produce autism and epilepsy in offspring. These combinations also result in marked brain inflammation, a reaction of the immune system thought to contribute to both epilepsy and autism. They developed a rat model of epilepsy/autism to study the effects of combined environmental inflammatory factors, to establish human maternal guidelines and to explore anti-inflammatory strategies to prevent or reduce this severe neurological syndrome.



CURE grant award Isaiah Stone Foundation Award
Poduri

Annapurna Poduri, MD, MPH
Children’s Hospital Boston

“Genetics of Sudden Unexpected Death in Pediatrics and Hippocampal Pathology—A Novel Entity Linking SIDS and SUDC to Epilepsy”

Can genetics determine which children are at risk of sudden death? Sudden unexpected death in the young, which includes SIDS (Sudden Infant Death Syndrome), SUDEP (Sudden Unexpected Death in Epilepsy), and SUDC (Sudden Unexpected Death in Childhood), accounts for more deaths in the United States than all childhood cancers combined. The causes of death and how to identify those at risk remain largely unknown. Evidence suggests a biological link between SIDS, SUDEP, and SUDC. All display epilepsy-related defects in the hippocampus, a critical region of the brain involved in seizures, as well as a higher personal and familial rate of febrile seizures. The goal of this project is to find genes that underlie the hippocampal defects seen in each of these disorders, and thereby understand the biology of how SIDS, SUDEP, SUDC and febrile seizures are linked. This work may identify genetic and brain imaging biomarkers that can help determine who among children with febrile seizures, and their siblings, are at risk of death so that prevention strategies can be implemented.



Roopra

Avtar Roopra, PhD
University of Wisconsin – Madison

“Epigenetic Regulation of Tonic Inhibition in Epilepsy”

Epilepsy can be either acquired or genetic. In both cases, seizures can trigger long-term changes such as an imbalance between neuronal excitation and inhibition. Inhibition comes in two major flavors, both mediated by the neurotransmitter GABA acting through GABAA receptors: a) fast and brief synaptic transmission and b) constant activation of receptors by low ambient concentrations of GABA (i.e., “tonic inhibition”). A growing wealth of evidence shows that increases or decreases in tonic inhibition are associated with epilepsy; however, what controls the levels of genes important for tonic inhibition is unknown. All genes are controlled by transcription factors (TFs). Some TFs control thousands of genes and are often called “Master Regulators”. Dr. Roopra’s data suggests that a Master Regulator called Polycomb (Pc) is induced in multiple epilepsy models and suppresses a GABAA receptor gene called delta that is normally required for tonic inhibition. Importantly, there are drugs already in clinical trials for other diseases that could be re-purposed to suppress Pc and restore GABA-delta expression and thus restore healthy levels of tonic inhibition.



Sainju

Rup Kamal Sainju, MD
University of Iowa – Iowa City

“Abnormal ventilatory response to CO2 in epilepsy patients: a potential biomarker for seizure induced respiratory depression & modification by SSRI”

Specific mechanisms of death in “Sudden unexpected death in epilepsy” (SUDEP) are not well understood, but seizure related breathing problems are probably important in many cases. Dr. Sainju’s team will investigate whether patients who have a depressed interictal breathing response to rising carbon dioxide levels in the blood are more likely to have seizure related breathing abnormalities. They also plan to test the effect of fluoxetine in reversing this depressed breathing response and in reducing the severity of seizure related breathing abnormalities. This study may identify a new biomarker for patients at high risk for SUDEP and a novel treatment to be tested in future studies.



CURE grant award The Cameron Benninghoven Award
Simeone

Kristina Simeone, PhD
Creighton University

“Orexin triggers autonomic destabilization in SUDEP”

Dr. Simeone’s overall goals are to determine a central trigger of SUDEP, identify novel biomarkers to better identify risk for and imminence of SUDEP, and identify a treatment to postpone and ultimately prevent SUDEP. Key events that lead to SUDEP include cardiac and respiratory failure. Failure of these two systems is attributed to a destabilization of the autonomic nervous system. They hypothesize that a neuropeptide is a central lynchpin that over a lifetime gains influence and progressively destabilizes these autonomic cardiorespiratory responses and ultimately results in SUDEP.



Traynelis

Stephen Traynelis, PhD
Emory University

“Functional and Clinical Evaluation of NMDA Receptor Mutations in Epileptic Encephalopathy”

Dr. Traynelis’ group will test whether FDA-approved drugs that block NMDA receptors (NMDARs) reduce the seizure burden in children with overactive NMDARs due to GRIN mutations. They will evaluate the effect of NMDAR mutations on receptor function and the sensitivity in vitro to candidate drugs (such as memantine), which will inform the use of these agents in patients. They will monitor seizure type and frequency, EEG, and developmental assessment before and after off-label treatment with FDA-approved NMDAR inhibitors. The project has the potential to impact the lives of patients whose seizures are refractory to current therapies by providing personalized, targeted therapy.



Wagner

Amy Wagner, MD
University of Pittsburgh

“Genetic Influences on Epileptogenesis and Biosusceptibility to Post-traumatic Epilepsy”

Traumatic brain injury (TBI) is an ongoing public health challenge, and post-traumatic epilepsy (PTE) negatively impacts the recovery of individuals already coping with TBI and its comorbidities. PTE accounts for 20% of those with symptomatic seizures and 5% of those with any seizure in the general population. Despite these numbers, there are no accepted means of identifying who is at risk for developing PTE following injury. Dr. Wagner’s team plans to conduct studies that will have a transformative impact on treatment and prevention of PTE for individuals with both civilian and military TBI. They are partnering with the principal investigator of the Vietnam Veterans Head Injury Study (VHIS) to evaluate currently identified genetic variants in the form of a “gene risk score” (GRS) that will help quantify how genetics influence PTE risk. The GRS can be used to help identify who is at greatest risk for PTE and it can be used in partnership with clinical treatment studies to evaluate how personal genetics might influence treatment response and PTE prevention measures.



CURE grant award In Honor of Felix Henry
Xue

Mingshan Xue, PhD
Baylor College of Medicine

“Novel Models of Epileptic Encephalopathies”

Epileptic encephalopathies are a group of devastating pediatric neurological disorders, manifesting with aggressive seizures and significant neurological comorbidities. Despite the rapid progress in identifying the genetic causes of epileptic encephalopathies, our understanding of the underlying pathogeneses remains limited, which hinders the development of new therapeutic interventions. Dr. Xue’s team aims to generate and validate novel mouse models of epileptic encephalopathies. They will utilize these models to understand how genetic deficits alter synaptic functions and cortical circuits, and to determine the reversibility of the neurological phenotypes in adulthood.




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.

Soria

Rene Barro Soria, PhD
University of Miami

“Molecular mechanisms of epilepsy-causing mutations in the IKM channel: anti-epileptic effect of polyunsaturated fatty acids (PUFAs) variants”

Epilepsy is characterized by abnormal neuronal activity in the brain. Mutations in the potassium channel regulating the excitability of neurons, the IKM channel, have been causally linked to some epilepsies. How mutations of IKM channels (channelopathies) cause epilepsy remains unknown. At present, available anti-epileptic drugs fail to control more than 30% of patients suffering from epilepsy. Therefore, there is a need to understand the molecular basis of the disease to create strategies to develop new anti-epileptic drugs. The goals of the present research project are a) to define the molecular basis of voltage activation of IKM channels, to understand the mechanisms by which epilepsy causing mutations affect IKM channels function and b) to design new drugs for the treatment of these IKM channelopathies. In the future, tailoring antiepileptic therapies to specific mutations will greatly improve the clinical outcome of treatments for each patient.



Cain

Stuart Cain, PhD
University of British Columbia

“Examining the link between seizures, spreading depression and SUDEP”

Spreading depression is a phenomenon in which brain cells go completely silent, and it is thought that if this spreads into the brainstem, it can lead to death. The goals of this project are to define the specific brain regions that promote spreading depression into the brainstem and to test whether spreading depression and death can be affected by a new, experimental, seizure-suppressing drug. If successful, this work will confirm that fatality in epilepsy is caused by spread of disabled nerve cell activity to the brainstem, either as a result of or accompanied by severe seizures. It will also define a set of brain regions and underlying mechanisms that cause fatality and potentially identify a new drug for the prevention of SUDEP. Knowledge of the key brain regions that cause spread of nerve cell inactivity and the underlying control mechanisms will allow for drug discovery targeting only those brain areas affected, thereby limiting side effects.



Ewell

Laura Ewell, PhD
University of California, San Diego

“Pediatric epilepsies: microRNAs determine network excitability during development”

Pediatric epilepsies arise when the assembling of the brain goes wrong, the mechanisms for suppressing activity are not in place, and neurons become hyperexcitable. To cure these diseases we need to identify and better understand the master regulators that instruct brain assembly and potentially fail in epilepsies. MicroRNAs (miRs) are great candidates. They coordinate complex developmental processes and are altered in patients with epilepsy. Dr. Ewell’s team is studying the role of a miR that is abundant in inhibitory interneurons. They hypothesize that it supports the development of inhibitory neurons in networks, enabling interneurons to function properly. Functional inhibition is crucial for protecting networks against hyperexcitability, so they hope that understanding miR regulation of inhibition during development will lead to powerful drug targets to cure pediatric epilepsies.



Myers

Kenneth Myers, MD, PhD
University of Melbourne/Austin Health

“Genetic Prediction of Drug Response in Childhood Absence Epilepsy”

The primary goal of this work is to assess whether the genetics of individuals with a specific seizure disorder, Childhood Absence Epilepsy (CAE), can be used to predict what medication will best control their seizures. They will study genes related to communication between two parts of the brain that are known to be disrupted in CAE. The ultimate goal is to generate data that can be used to design a rapid genetic testing protocol that will help doctors choose a medication for CAE based on an individual’s genetics, taking a step closer to precision medicine. If successful, this project will demonstrate that treatment of a common epilepsy syndrome can be enhanced using genetic testing. For the children with CAE, this will mean faster control of seizures and fewer side effects. This research approach can then be applied to other genetic epilepsy syndromes, and in the long term, should improve the treatment of all people with 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.

Biagioli

Marta Biagioli, PhD
University of Trento, Trento, Italy

“SINEUPs Technology: a New Route to Treat Haploinsufficiency-Induced Epilepsy”

Genetic mutations account for the majority of epilepsies. Recently, a new gene, CHD2, has been highlighted as an important risk factor. All the CHD2 characterized mutations are disruptive, mostly causing reduced protein levels in the brain, and this is thought to contribute to the development of epilepsy. Dr. Biagioli’s recent discovery of a way to increase the expression of target proteins laid the basis of a new technology called SINEUP. This technology holds promise for rescuing disorders associated with protein level reductions as a consequence of genetic mutations. This proposal aims to demonstrate how SINEUP can rescue the protein deficit and treat the disease. This will be the first step towards the development of a new type of therapy to potentially impact many presently incurable genetic diseases with implications beyond CHD2 and epilepsy.



CURE grant award Julie's Hope Award
Mallamaci

Antonello Mallamaci, PhD
Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy

“Scalable transcriptional-translational therapy of epileptogenic gene haploinsufficiencies”

More than one hundred distinct gene losses may lead to epilepsy. As these pathologies are individually rare and the defective genes are implicated in a variety of cellular processes, the development of effective cures is hard, due to the complexity of the problem and the huge economic investments needed. We will try to fix this issue via multilevel stimulation of the spared gene copy, by three novel enabling technologies, which comply with endogenous gene regulation needed for neuronal function. If successful, this approach will be exploitable for scalable, personalized cures of epileptogenic gene loss.



CURE grant award Vivian L. Cotton Award
Nishiyama

Akiko Nishiyama, MD, PhD
University of Connecticut

“Reprogramming NG2 glial cells into inhibitory neurons in an epilepsy model”

NG2 glial cells are non-neuronal cells that are widely distributed in the adult brain. Their primary role is to generate oligodendrocytes that make myelin to allow fast conduction of electrical signals, but they also communicate with neurons in the neural network. Dr. Nishiyama has found that NG2 cells can be reprogrammed to become inhibitory interneurons in culture by a transcription factor. The goal of this project is to test the potential of local NG2 glial cells as a source of functionally active interneurons in the seizure environment using a mouse model of temporal lobe epilepsy.



Staley

Kevin Staley, MD
Massachusetts General Hospital

“Epileptogenic neuronal homeostasis after injury: focus on neurofilaments”

Chloride ions carry most of the signals that stop seizures in the brain. However, when the anticonvulsant signaling molecule GABA activates chloride signaling, the expected anticonvulsant effect does not always occur. Dr. Staley's team proposes that brain cells change their chloride content in response to a variety of conditions. They will ask if brain cells vary their local chloride content by using "salt substitutes". Salt substitutes are molecules that carry the same amount of electrical charge as chloride, but are unable to stimulate the action normally associated with chloride. The team will focus on actin, a highly charged structural molecule that likely can act as a "salt substitute". If they find that brain cells alter the effect of GABA by changing local actin, they can target this mechanism to treat epilepsy. Many of these mechanisms are already well-studied in other diseases and could be readily refocused to treat uncontrollable epilepsy.



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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