Introduction to gene therapy in neurological surgery

Abstract

Gene therapy is an exciting new discipline in which neurosurgery and neurosurgeons can have a direct impact on both patient care and emerging scientific developments. Unlike other organs, the brain is unique in that it has a blood–brain barrier, often preventing efficient systemic gene delivery to the area of interest. Therefore, not only is gene delivery required, but it will often need to be accomplished in a local and specific manner. Although brain neoplasms have been the most commonly studied application of genetic therapeutics in neurological surgery, there are many other potential applications of this technology to neurosurgical disorders, including spinal instability, neurodegenerative disease, neurogenetic diseases, central nervous system (CNS) injury, aneurysms, trauma, stroke, and epilepsy. As the field of gene therapy for the CNS develops from the preclinical setting to clinical trials to mainstream therapy, the need for safe and specific gene delivery will be increasingly apparent. Neurosurgeons are in an enviable position as there is nobody more qualified to address the issue of how a gene can be delivered to the central nervous system. Not only do we have the training to operate on the nervous system and its coverings, but we have the ability to recognize and take care of complications that may arise from these procedures. However, the neurosurgeon's role in gene therapy for the brain and spine should not be confined to gene delivery only. Instead, we also need to understand and have a role in deciding what genes could have therapeutic utility in our patients. Herein lies our challenge in gene therapy: how can we as neurosurgeons interface with our basic science colleagues to address rapidly all of the problems that are blocking the advancement of nucleic acid therapeutics into the clinical setting.