Degeneration of intervertebral discs: current understanding of cellular and molecular events, and implications for novel therapies

Recent advances in surgical techniques have made it possible to study the changes that are known as degeneration of the intervertebral disc (IVD) in greater depth than ever before. This is an important area of study because degeneration of the lumbar IVDs is associated, perhaps causally, with low back pain: one of the most common and debilitating conditions in the western world. The term degeneration implies an inevitable progression that is characteristic of wear-and-tear-associated conditions. However, modern research on human tissue has shown that this is not the case. Here, disruption of the micro-anatomy that is described as degeneration is an active process, which is probably regulated by locally produced cytokines. This one observation opens up the possibility of inhibiting or even reversing the processes of degeneration. The immediate question is how can the slowly progressive changes of degeneration be treated, particularly as connective tissue repair is thought to be a slow and highly regulated process. In this review, the possibility of using gene therapy as a single-shot, long-lasting therapeutic strategy is discussed, together with an outline of developments in this area to date.