Biologic modification of animal models of intervertebral disc degeneration

Intervertebral disc degeneration is a chronic process that can become manifest in clinical disorders such as idiopathic low back pain, sciatica, disc herniation, spinal stenosis, and myelopathy. The limited available treatment options (including discectomy and spinal fusion) for these and other disabling conditions that arise from intervertebral disc degeneration are highly invasive, achieve limited success, and only address acute symptoms while doing nothing to halt the process of degeneration. Although the precise pathophysiology of intervertebral disc degeneration has yet to be clearly delineated, the progressive decline in aggrecan, the primary proteoglycan of the nucleus pulposus, appears to be a final common pathway. Animal models as well as in vitro studies of the process of disc degeneration have yielded many potentially useful targets for the reversal of disc degeneration. One current research trend is the use of established animal models of disc degeneration to study the role of therapeutic modalities in reversing the process of degeneration, often with use of the delivery of genes or gene products that influence the anabolic and catabolic pathways of the disc. This article reviews the ability of gene-product delivery systems and gene therapy to alter biologic processes in animal models of disc degeneration and examines future trends in this field.