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.

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.

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.

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.

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.

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.

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.

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.