Gene therapy may represent an effective alternative to standard pharmacological approaches for certain forms of epilepsy. Currently, the best candidates for this therapeutic approach appear to be epilepsies characterized by a focal lesion. Gene therapy has been attempted to produce anti-epileptogenic (prevention of development of epilepsy in subjects at risk after having received an epileptogenic insult), anti-seizure (reduction of frequency and/or severity of seizures) and disease-modifying effects (alteration of the natural history of the disease). An example of anti-epileptogenic effects is a combination therapy based on the supplementation of the neurotrophic factors brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF-2). Anti-seizure effects have been obtained by increasing the strength of inhibitory signals (by supplementing specific GABAA receptor subunits or the inhibitory neuropeptides like galanin or neuropeptide Y) or by reducing the strength of excitatory signals (by knocking down NMDA receptor subunits) produced antiseizure effects. This review summarizes the results obtained to date using gene therapy in epilepsy models and discusses the challenges and the opportunities that this approach can offer for the treatment of human epilepsies.
Gene therapy for epilepsy.
SIMONATO, Michele
2013
Abstract
Gene therapy may represent an effective alternative to standard pharmacological approaches for certain forms of epilepsy. Currently, the best candidates for this therapeutic approach appear to be epilepsies characterized by a focal lesion. Gene therapy has been attempted to produce anti-epileptogenic (prevention of development of epilepsy in subjects at risk after having received an epileptogenic insult), anti-seizure (reduction of frequency and/or severity of seizures) and disease-modifying effects (alteration of the natural history of the disease). An example of anti-epileptogenic effects is a combination therapy based on the supplementation of the neurotrophic factors brain-derived neurotrophic factor (BDNF) and fibroblast growth factor-2 (FGF-2). Anti-seizure effects have been obtained by increasing the strength of inhibitory signals (by supplementing specific GABAA receptor subunits or the inhibitory neuropeptides like galanin or neuropeptide Y) or by reducing the strength of excitatory signals (by knocking down NMDA receptor subunits) produced antiseizure effects. This review summarizes the results obtained to date using gene therapy in epilepsy models and discusses the challenges and the opportunities that this approach can offer for the treatment of human epilepsies.I documenti in SFERA sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
