Investigation of vaccinia virus complement control protein as a potential therapeutic agent following traumatic spinal cord injury

Traumatic spinal cord injury (SCI) claims approximately 10,000 new victims every year in the United States alone. The injury primarily strikes those under the age of 30 years, often leading to a lifetime of pain, suffering, and disability. While the burdens of SCI undeniably fall chiefly upon the victim, society also pays a price, for the total annual medical expenditure in the U.S. designated for SCI care approaches {dollar}10 billion. The primary spinal cord injury is followed by a wave of secondary injury that can extend and exacerbate the original wound. The pathophysiological mechanisms underlying secondary injury have only recently come under close scrutiny, for the complexity of the various injury mechanisms and cellular interactions have resisted unraveling until the advent of modern research techniques.; Secondary injury mechanisms are known to involve hemorrhage, ischemia-reperfusion, excitotoxicity, demyelination, calcium mediated injury, disturbances in mitochondrial function, apoptosis and necrosis of neurons and oligodendrocytes, and inflammation, although the degree to which different events contribute to injury is subject to intense debate. However, inflammation is thought to play a major role in the broadening of damaging events.; Clinical therapeutic agents targeting SCI are sorely lacking, with only one agent, methylprednisolone, in widespread, albeit controversial, clinical use. Therefore our laboratory endeavored to evaluate the potential therapeutic benefits of immediate post-injury administration of the vaccinia virus complement control protein (VCP), a potent inhibitor of inflammation. VCP is able to inhibit the classical and alternative pathways of complement activation, has recently been shown to possess the ability to bind heparin, and was shown in this study to inhibit in vitro chemotaxis of monocytes.; Utilizing a common animal model of contusive SCI, motor function recovery tests, myeloperoxidase assays for neutrophil detection, and immunochemical stains for assessment of inflammatory and neuronal cell responses, we evaluated the effects of various doses of VCP injected directly into spinal cord tissue following injury. Results demonstrated that VCP administration is able to inhibit neutrophil and macrophage infiltration of injured tissue and improve hindlimb function within the first week of injury, establishing VCP as a worthy candidate for further investigation in the treatment of SCI.