Summary
Gene therapy offers exciting new options for treating epileptic seizures, and even for blocking the development of epilepsy (i.e., epileptogenesis) after a brain insult. Although the available studies provide interesting new data, the experiments discussed in this issue also have limitations and raise concerns. The criticisms offered in this commentary center around the nature of the experimental testing (e.g., changes in seizure threshold), the animal models (e.g., kindling), and the measures of epileptogenesis in those animal models with spontaneous seizures (e.g., the latent period after pilocarpine-induced status epilepticus). Another set of criticisms relate to the relative lack of positive controls showing that the actual mechanism purported to be activated via the gene-therapeutic approach has in fact been upregulated in the specific animals that show the hypothetical antiepileptic result. This commentary takes the con side in the debate, to generate constructive criticism to help direct future studies to provide increasingly stronger data to support the view that gene therapy approaches may be useful in the treatment of epilepsy.
Article PDF
Similar content being viewed by others
References
Lin EJD, Richichi C, Young D, Baer K, Vezzani A, During MJ. Recombinant AAV-mediated expression of galanin in rat hippocampus suppresses seizure development. Eur J Neurosci 2003; 18: 2087–2092.
Foti S, Haberman RP, Samulski RJ, McCown TJ. Adeno-associated virus-mediated expression and constitutive secretion of NPY or NPY13-36 suppresses seizure activity in vivo. Gene Ther 2007; 14: 1534–1536.
Richichi C, Lin EJD, Stefanin D, et al. Anticonvulsant and antiepileptogenic effects mediated by adeno-associated virus vector neuropeptide Y expression in the rat hippocampus. J Neurosci 2004;24: 3051–3059.
Walker MC, White HS, Sander JWAS. Disease modification in partial epilepsy. Brain 2002;125: 1937–1950.
Raol YH, Lund IV, Bandyopadhyay S, et al. Enhancing GABAA receptor α1 subunit levels in hippocampal dentate gyrus inhibits epilepsy development in an animal model of temporal lobe epilepsy. J Neurosci 2006;26: 11342–11346.
Lehmkuhle MJ, Thomson KE, Scheerlinck P, Pouliot W, Greger B, Dudek FE. A simple quantitative method for analyzing electrographic status epilepticus in rats. J Neurophysiol 2009 Jan. 7 (Epub ahead of print).
Bertram EH, Cornett J. The ontogeny of seizures in a rat model of limbic epilepsy: evidence for a kindling process in the development of chronic spontaneous seizures. Brain Res 1993;625: 295–300.
Bertram EH, Cornett JF. The evolution of a rat model of chronic spontaneous limbic seizures. Brain Res 1994;661: 157–162.
Williams PA, White AM, Clark S, Ferraro DJ, Swiercz W, Staley KJ, Dudek FE. Development of spontaneous recurrent seizures after kainate-induced status epilepticus. J Neurosci 2009;29: 2103–2122.
Noè F, Pool AH, Nissinen J, et al. Neuropeptide Y gene therapy decreases chronic spontaneous seizures in a rat model of temporal lobe epilepsy. Brain 2008;131: 1506–1515.
Thompson K. Transplantation of GABA-producing cells for seizure control in models of temporal lobe epilepsy. Neurotherapeutics 2009;6: 284–294.
Riban V, Fitzsimons HL, During MJ. Gene therapy in epilepsy. Epilepsia 2009;50: 24–32.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Dudek, F.E. Commentary: A skeptical view of experimental gene therapy to block epileptogenesis. Neurotherapeutics 6, 319–322 (2009). https://doi.org/10.1016/j.nurt.2009.01.020
Issue Date:
DOI: https://doi.org/10.1016/j.nurt.2009.01.020