Spinal Cord Injury
Spinal cord injury that interrupts descending motor pathways and ascending sensory pathways is a significant cause of disability in the veteran population. In studies funded by the Department of Veterans Affairs, we are using HSV-mediated gene transfer to express genes locally in the spinal cord to enhance cell survival and long-tract regeneration with the ultimate goal of improving functional outcome after spinal cord injury.
In published experiments we have examined the effects of HSV-based vectors expressing the anti-apoptotic peptide Bcl-2 and the glial cell derived neurotrophic factor (GDNF). More recently, we have demonstrated improved behavioral outcomes with vectors expressing the neuroprotective peptides erythropoietin and vascular endothelial growth factor. Ongoing studies are designed to examine the neuroprotective and regeneration-favoring potential of HSV vectors expressing interleukin-10 or a fragment of the NOGO receptor to interfere with NOGO signaling.
In other studies we are using peripheral delivery of HSV vectors to transduce DRG neurons to modify below-level pain after spinal cord injury using vectors that result in the release of inhibitory neurotransmitters (i.e. gamma amino butyric acid) as well as anti-inflammatory peptides (tumor necrosis factor alpha soluble receptor and interleukin-4).