Peel AL, Klein RL. 2.5 million Americans (Hirtz, et al., 2007) and 50 million people worldwide (Hauser, Igf1r 1990) who suffer from epilepsy. With this disease also comes a tremendous financial burden; epilepsy associated medical costs, lost or reduced income and decreased production result in an estimated annual cost to the United States of $15.5 billion (Shafer and Begley, 2000). Although current anti-epileptic medication effectively controls seizures in approximately 70% of people receiving optimal care, these medications are inadequate for the remaining 30% of patients (Cascino, 2008, Kwan and Brodie, 2000). Fewer than 10% of patients with drug refractory epilepsy are considered for surgical resection (Engel, et al., 1992, Sander, 1993, Shafer, et al., 1988, Siegel, 2004), leaving many epilepsy sufferers with no therapeutic recourse. Limited progress has been made since the early 1990s in the development of antiepileptic drugs with improved efficacy or tolerability (Loscher and Schmidt, 2011). Moreover the number of patients with drug-resistant epilepsies has not decreased, (Loscher and Leppik, 2002) providing an impetus for development of the new, more effective anti-epileptic drug treatments. Gene therapy has significantly advanced in both preclinical and clinical research venues for the study and treatment of a wide array of human diseases, including disorders of the central nervous system (CNS). Mounting clinical successes (Bainbridge, et al., 2008, Cideciyan, et al., 2009) and encouraging security, tolerability and longevity findings in human (Kaplitt, et al., 2007) and non-human primate (Hadaczek, et al., 2010) CNS have solidified gene therapy as a realistic alternative to small molecule treatments. The CNS has confirmed quite permissive to viral vector gene transfer and expression for many of the conventional delivery vectors. Adenovirus, herpes simplex virus, lentivirus, and adeno-associated computer virus are the most frequently utilized viral vectors for brain and spinal cord gene delivery. While each confers unique strengths and weaknesses many of these viral vectors support long-term, non-toxic delivery of foreign genetic information to host cells. Common uses of viral vectors include replacing deleted or mutated genes, targeted knockdown of dysfunctional or pathogenic genes, cellular expression of therapeutic proteins and expression or knockdown of a particular gene for molecular genetics studies. This review addresses the state of gene therapy research for treating epilepsy. We begin by describing the major gene transfer strategies for treatment, including strategies that mimic or bear similarity to the currently available major small molecule anticonvulsants, and also those strategies that are less standard. Epilepsy and seizure disorders are analyzed using a limited quantity of common epilepsy models intended to MIF Antagonist MIF Antagonist mimic selective aspects of clinical disease. Currently, most epilepsy gene therapy studies involve limbic brain structures such as the hippocampus, piriform cortex or entorhinal cortex where seizure activity is usually induced by kainic acid, pilocarpine or electrical kindling activation. These animal models are intended to be reflective of human temporal lobe epilepsy. Still other studies have involved non-limbic brain areas that support focal seizure activity. The first half of this MIF Antagonist review explains the strategies and results of viral MIF Antagonist vector gene transfer preclinical epilepsy studies The second half of this evaluate explores the major considerations and current difficulties in working with CNS gene transfer. Gene transfer based on pharmacological anti-epilepsy targets Unlike genetic disorders such as hemophilia or Duchennes muscular dystrophy, for which gene therapy offers promise of specific gene correction (Manno, et al., 2006, Mendell, et al., 2010), intractable epilepsy often occurs without any known genetic linkage. While you will find examples of familial mutations resulting in seizure disorders (e.g. sodium channel, voltage-gated, type I, alpha subunit [SCN1A] mutations), most intractable epilepsy cases are idiopathic. Thus, the predominant therapeutic strategy has focused upon attenuating the seizures through manipulation of excitatory or inhibitory function in the CNS. Certainly, one rational focus for gene therapy has been MIF Antagonist to recapitulate or.