This chapter reviews the selection of the "therapeutic" genes delivered into the rodent brain for studying their ability to inhibit seizures and delay epileptogenesis in vivo experimental models of epilepsy. Important aspects that contribute to determine the success or failure of a gene therapy approach are also described, such as the methods of gene delivery, strategies for improving cell transfection and neuronal expression, regulation of gene expression, and possible host tissue reactions to the transgene. The choice of therapeutic genes is a crucial aspect, which should take into account the molecular basis of the CNS disorder. Several potentially suitable targets for epilepsy can be envisaged based on the available knowledge of the genes and related proteins involved in the susceptibility to seizure, their onset and generalization. At some stage prior to resective surgery, the patients could have vector infusion into the focus and the efficacy of the vector could be evaluated over a period of months before tissue resection. This approach gives important insights into the level of expression of the transgene in the surgically removed epileptic tissue specimen. Once the gene therapy effectiveness is demonstrated in epileptic tissues, and the safety concerns are adequately addressed in primate models, then the therapeutic potential of this novel and an alternative approach is applied to the clinic for controlling otherwise pharmacologically intractable seizures.
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)