Efficacy of Erythropoietin (EPO) and EPO Analogues in the Treatment of Epilepsy

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DESCRIPTION (provided by applicant): A large proportion of patients with temporal lobe epilepsy (TLE) does not respond to currently available medications, and in the course of the disease develop injury to the brain. This application proposes to determine the efficacy of erythropoietin (EPO) as a therapeutic agent in treating TLE. Recombinant human erythropoietin (rhEPO) is an already FDA approved drug for the treatment of anemia, which has a well-documented safety record. Erythropoietin has also been demonstrated to have neuroprotective effects in a number of neurological conditions. This proposal will test the efficacy of rhEPO (which in high doses may have erythropoietic side-effects) and several erythropoietic analogues - carbamylated erythropoietin, asialoerythropoietin, and APA290 a tissue protective molecule with EPO like properties (all of which do not have an erythropoietic effect) on the suppression of seizures and neuroprotection in a pilocarpine-induced seizure model in rats. The principal aim is to identify the best molecule that can ameliorate seizures and give neuroprotection at doses that do not have erythropoietic effects. NAA spectroscopic imaging during the course of treatment will be carried out to determine a non-invasive method for following the effectiveness of these drugs in intended future translational studies in humans. If proven efficacious, these molecules can in future be taken to preclinical and clinical trials for treatment of TLE and even other seizure disorders. Public Health Relevance: This study with explore the efficacy of recombinant human erythropoietin and new erythropoietin analogues which have neuroprotective but not erythropoietic effects in reducing or eliminating seizures in the pilocarpine induced seizures in rats. It is an exploratory study towards translation to human use.