Gene Therapy Approaches for Neuroprotection and Axonal Regeneration after Spinal Cord and Spinal Root Injury

Recent understanding in pathophysiological mechanisms of spinal cord and spinal root injuries has facilitated the development of new strategies to promote neural repair. Gene therapy approaches have been viewed as the ideal means to achieve long-term local delivery of therapeutic molecules in the central nervous system (CNS). Ex vivo gene delivery offers the additional advantage of providing cellular support for regenerating axons. In this review, we summarize the studies on viral vector-mediated gene delivery to spinal cord in animal models, both in vivo and ex vivo. Most of the studies reported so far are aimed at delivery of various growth factors, such as neurotrophins and neuropoietic cytokines. Other molecules tested include those that interfere with intracellular processes to prevent cell death, or increase intrinsic regenerating state of injured neurons, or modify the CNS environment to make it permissive for axon growth. Several different combinatorial strategies involving gene delivery are also discussed as it has been recognized that successful neural repair may require the synergistic actions of multiple therapeutic managements.