Nathan Fountain, M.D., Director, F.E. Dreifuss Comprehensive Epilepsy Program, University of Virginia and Thomas Sutula, M.D., Ph.D., Detling Professor and Chair, University of Wisconsin-Madison and Co-founder, Chief Technical Officer of NeuroGenomeX, Inc., will be assessing the clinical activity of 2-deoxy-D-glucose (2DG) in reducing seizure frequency in subjects with a history of frequent seizures. The investigators will use the grant funding in an initial Phase II safety, tolerability and proof-of-principle clinical study of 2DG. By investigating the mechanisms of anticonvulsant action of the ketogenic diet (isocaloric replacement of carbohydrates by fats and proteins), researchers identified the inhibition of glycolysis as a novel mechanism of anticonvulsant and antiepileptic action. Administration of 2DG, a known inhibitor of glycolysis, also demonstrated acute anticonvulsant action in early evaluation, and had pronounced anticonvulsant and antiepileptic effects in preclinical studies. Importantly, the pattern of anticonvulsant efficacy of 2DG in screening models is distinctive as compared to currently available drugs. 2DG has a well-established preclinical efficacy and toxicity profile, with decades of use as an imaging tracer, as well as safety established during previous Phase I/II human clinical trials for cancer.
Demonstration of efficacy in this initial clinical proof-of-principle trial would be a substantial milestone in the development of 2DG as a therapy for seizure disorders by adding evidence of efficacy and safety to current preclinical evidence in epilepsy animal models.
New Therapeutic with Promise for Neuroprotection and Treatment in Neonatal Care
A University of Minnesota research team headed by James Cloyd, PharmD, Professor of Experimental & Clinical Pharmacology, Lawrence C. Weaver Endowed Chair-Orphan Drug Development, and Director, Center for Orphan Drug Research, received funding to support the study of an intravenous formulation of the anticonvulsant Topiramate (TPM), a drug that has demonstrated important neuroprotective properties in preclinical models. Topiramate, in its oral formulation, is currently prescribed to treat epilepsy in children and adults. In this program, researchers are pursuing the long-term goal of developing a novel, FDA-approved, intravenous topiramate for the neuroprotection and treatment of seizures in neonates with hypoxic brain injuries. An estimated 15,000 neonates experience seizures, which cause brain injury and death. Current therapy is only partially effective and is associated with serious adverse effects. The National Institutes of Neurological Disorders and Stroke has identified improved treatment of neonatal seizures as a significant unmet need.
Grant funding will be applied to conduct a safety and pharmacokinetics study of a new IV and oral topiramate in healthy volunteers.
SOURCE Epilepsy Therapy Project