Grant: Randomized, Double Blind Parallel Trial of External Trigeminal Nerve Stimulation for Intractable Epilepsy
UCLA School of Medicine
Los Angeles, California
Christopher DeGiorgio, M.D., Jason Soss, M.D., and Lara Schrader, M.D., of the UCLA Department of Neurology Seizure Disorders Center, and Olive View-UCLA Medical Center, in collaboration with Todd Whitehurst, M.D., of Advanced Bionics, Inc., were the recipients of a grant to perform a randomized trial of Trigeminal Nerve Stimulation (TNS) in people with poorly controlled epilepsy. Christianne Heck, M.D., of the USC-Keck School of medicine, also will be a co-investigator in this study. TNS is a promising new therapy that involves the external electrical stimulation of a nerve located above the eyes and over the forehead. Neurostimulation is a promising alternative for patients who have failed medical therapy and who are not surgical candidates. Stimulating the trigeminal nerve has several theoretical advantages: it is safe, low cost, and non-invasive. It can easily be performed prior to implantation of a permanent device to determine efficacy. In animals, TNS has a strong antiepileptic effect. In a pilot human study, TNS was safe and well tolerated; in addition, 57% of subjects had a >50% reduction in seizures. This grant will fund a double-blind clinical trial in 50 subjects. It will accelerate development of this exciting and novel therapy, which if successful, could make an innovative therapy available to people with epilepsy worldwide.
December 2007: New Therapy and Milken Family Foundation Grant Award
Grant: T-type Calcium Channel Antagonists as Novel AEDS
Baylor College of Medicine
Neuromed Pharmaceuticals Ltd
Vancouver, British Columbia Jeffrey L. Noebels, M.D., Ph.D., Professor of Neurology, Neuroscience, and Molecular and Human Genetics, Department of Neurology, Baylor College of Medicine, and Elizabeth Tringham, Ph.D., Project Leader for Epilepsy Discovery Efforts, Neuromed Pharmaceuticals, Ltd., received a grant to pursue the development of selective T-type calcium channel blockers as potential anti-epileptic drugs. Their research is based on evidence that generalized spike-wave absence seizures arise from currents in the brain mediated by the low threshold T-type calcium ion channel, and that these seizures are suppressed when this channel is absent or the current is pharmacologically reduced. This drug discovery project will screen a new class of highly potent and selective T-type calcium ion channel blockers for efficacy in single gene mouse mutant models of human spike-wave absence and temporal lobe epilepsy, with the goal of showing a superior anti-absence profile with fewer side effects than with current therapies for these conditions.
December 2007: Milken Family Foundation Translational Research Award
Grant: Pilot Safety Study Evaluating Hippocampal NPY Gene Transfer in Subject with Intractable Mesial Temporal Lobe Epilepsy
The Ohio State University
Fort Lee, New Jersey Matthew J. During, M.D., Professor and Director, The Ohio State University Human Cancer Genetics Program, and Neurologix, Inc., are the recipients of a grant to conduct a pilot study to inhibit seizures caused by temporal lobe epilepsy and to reduce the invasiveness of current surgical treatment approaches by targeting the hippocampus of the brain, and delivering healthy genes where defective ones are causing the central nervous system disorder. In particular, Dr. During and Neurologix will seek to deliver the human Neuropeptide Y (NPY) gene, one of the brain's endogenous anticonvulsants, to neurons in the hippocampus where NPY will act on receptors to inhibit the brain over-activity that occurs during seizures. This approach builds on experience Neurologix has gained through its similar gene transfer approach to treating Parkinson's disease in a Phase 1 clinical trial that demonstrated safety, tolerability and efficacy.
June 2007: New Therapy Grant Awards
Grant: Closed-looped microstimulation with multi-electrode arrays to suppress epileptic seizures Emory University School of Medicine Atlanta, Georgia
Robert E. Gross, M.D., Ph.D., Assistant Professor, Departments of Neurosurgery and Neurology, Emory University School of Medicine, and Steve M. Potter, Ph.D., Assistant Professor, Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, are the recipients of a grant for the development of a novel electrical stimulation approach that directly controls the activity of the brain to attain a more stable state from which seizures will not arise. By continuously controlling the activity of epileptogenic brain areas with distributed low-voltage stimulation, the researchers have shown that small arrays of multiple electrodes can completely suppress epileptic activity in cultured brain tissue. They hope to maintain the brain in a seizure-free or seizure-resistant state, therefore bypassing the need to detect or prevent seizures, and are investigating this treatment in animal models of epilepsy. Funding for this program was made possible in part through a gift from the Patricia Bowman Terwilliger Family Foundation Charitable Trust.
Grant: Multi-scale human electrophysiology and stimulation Mayo Clinic Rochester, Minnesota
Gregory A. Worrell, M.D., Ph.D., Associate Professor of Neurology, Mayo Clinic, received a grant to develop an electrophysiology platform for multi-scale EEG and stimulation experiments. Dr. Worrell and his research team have developed an electroencephalography (EEG) recording and stimulation approach that facilitates investigation across the range of spatiotemporal scales involved in the generation of seizures. They have recently identified a novel electrographic signature of epileptogenic brain that falls outside the spatiotemporal range of conventional intracranial EEG, and that may represent a precursor of seizure generation. They anticipate that their multi-scale EEG and stimulation approach will improve the efficacy of epilepsy surgery and therapeutic brain stimulation.
Grant: The development of intravenous topiramate for neuroprotection and seizure control in neonates University of Minnesota Minneapolis, Minnesota
James C. Cloyd, PharmD, Professor and Director, Epilepsy Research & Education Program, University of Minnesota, is the recipient of a grant to pursue the development of an intravenous (IV) formulation of topiramate to bring a well-established and effective medication to a new therapeutic indication: neonatal seizures. Neonatal seizures, for which there are limited therapeutic options, can result in impairment in development, cognition and potentially harmful side effects to the developing brain. Laboratory studies offer compelling evidence that topiramate, an effective anti-epileptic drug with a good safety record in children over two years of age and adults, could substantially improve the management of seizures in newborn infants. An IV formulation would be required to treat neonates because of the need to precisely control drug concentrations, and no IV topiramate currently exists.