Chapter 21 - Gene Therapy for Spinal Cord Injury

Abstract

This chapter reviews the steady advances that have been made in neuroregeneration research with the development of advanced gene and cell therapy to promote regeneration in animal models for spinal cord injury (SCI). It also includes a brief description of the pathophysiology of SCI and the predominantly used animal models. Spinal cord repair strategies comprise a multi-factorial approach addressing several issues, including the optimization of survival and function of the spared central nervous system neurons and the modulation of trophic and inhibitory influences to promote and guide axonal regrowth. Viral vector-mediated transfer of neurotrophic factor genes by direct vector injections is emerging as a novel and effective strategy to express neurotrophic proteins in the injured nervous system, including the spinal cord. Ex vivo transfer of neurotrophic factor genes is additionally explored a way to more efficiently bridge lesion cavities with cellular implants for axonal regeneration. Several viral vector systems, based on herpes simplex virus, adenovirus, adeno-associated virus, lentivirus and moloney leukemia virus have been employed. The genetic modification of fibroblasts, Schwann cells, olfactory ensheathing glia cells and stem cells, prior to implantation to the injured spinal cord has resulted in improved cellular nerve guides. The developed therapy includes a combination of growth-promoting molecules either delivered via genetically modified cells or by direct gene transfer as discussed in this review and the neutralization of outgrowth inhibitory factors present in central nervous system myelin and in the neural scar.