Neuropeptide gene therapy for epilepsy: viral vectors, stem cells and neurogenesis

Abstract

Gene therapy for epilepsy is a relatively novel concept compared with previous approaches, which have relied on primary embryonic cells to deliver gene products of interest into localized brain regions. In vivo and ex vivo gene transfer offer promising, but yet insufficiently explored, possibilities to inhibit seizures, either by genetically modifying postmitotic neurons of the brain using viral vectors, or by transplanting genetically modified and in vitro tested cell lines, particularly stem cell lines, to produce and release gene products of interest. In this regard, neuropeptides are discussed as emerging candidates for such gene therapy approaches. Selective modification of newly generated neurons in the dentate gyrus by retroviral vector-based gene delivery opens novel possibilities in gene therapy for epilepsy. However, the limited number of new neurons targeted remains a main obstacle. Despite its early stage, gene therapy for epilepsy might not be a remote prospect for clinical trials, particularly in patients with intractable temporal lobe epilepsy. Ex vivo gene transfer using encapsulated genetically modified cells could be of particular value for such initial trials.