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Gene Therapy of Focal-Onset Epilepsy Using Adeno-Associated Virus Vector-Mediated Overexpression of Neuropeptide Y 

Gene Therapy of Focal-Onset Epilepsy Using Adeno-Associated Virus Vector-Mediated Overexpression of Neuropeptide Y
Chapter:
Gene Therapy of Focal-Onset Epilepsy Using Adeno-Associated Virus Vector-Mediated Overexpression of Neuropeptide Y
Author(s):

Francesco M. Noè

, Andreas T. Sørensen

, Merab Kokaia

, and Annamaria Vezzani

DOI:
10.1093/med/9780199746545.003.0089
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date: 25 September 2018

Although various new antiepileptic drugs (AEDs) with diverse mechanisms of action have been developed in the last 15 years with improved tolerability and pharmacokinetic properties,1,2 there has been relatively little improvement in their ability to control pharmacoresistant epilepsies compared to traditional AEDs. Thus, about 30% of patients with epilepsy still have seizures that are resistant to available AEDs. Drug-resistant epileptic patients are considered for surgical resection of the epileptic focus: this invasive procedure, however, is suitable only for a minority of them and results in complete control of epilepsy (seizure freedom without AEDs) in about 30% to 50% of cases, according to a 5- to 10-year follow-up study.3 Additionally, most AEDs provide symptomatic suppression of seizures without apparently interfering with the mechanisms involved in the epileptic process.4,5 Currently, AEDs mainly target neurotransmitter receptors, mechanisms of neurotransmitter release or reuptake, or ion channels.1 There is therefore an urgent need to find novel treatment strategies, particularly for the most refractory forms, such as temporal lobe epilepsy (TLE). 4,6 As an alternative approach to pharmacotherapy, preclinical studies in models of seizures and epilepsy are addressing the possibility of suppressing seizures by inducing the overexpression of neuromodulatory molecules in the area(s) of seizure origin or propagation. This may be achieved using gene therapy that has been developed, and clinically applied, in other neurological disorders.7–12 The intent of experimental studies is to establish the proof-of-concept evidence that gene therapy may be envisioned as a novel therapeutic approach to control drug-resistant seizures in focal-onset epilepsies.

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