Potential Biologic Therapies for the Intervertebral Disc - Protein

Potential Biologic Therapies for the Intervertebral Disc
2006
Christopher Evans, PhD, DSc
JB&JS
The author did not receive grants or outside funding in support of his research for or preparation of this manuscript. The author received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity (Dr. Evans is on the scientific advisory board of TissueGene Inc. and Orthogen AG). No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the author is affiliated or associated.
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Biology offers several strategies for restoring the degenerating disc, including the use of recombinant or natural proteins that increase matrix accumulation and assembly, enhance the number of disc cells, or in other ways lead to restoration of the native healthy disc. Recombinant bone morphogenetic protein-7 (osteogenic protein-1) shows promise in this regard. Other growth factors, as well as cytokine antagonists such as the interleukin-1 receptor antagonist, are also good candidates. Because disc degeneration is a chronic, progressive disorder occurring over many years, it is likely that growth factors and other therapeutic proteins will need to be present in the disc for extended periods of time. The intradiscal injection of recombinant or natural proteins is unlikely to fulfill this requirement. In this scenario, the delivery of genes that encode the protein in question may provide a better delivery system. Kang and associates have pioneered this strategy, demonstrating the responsiveness of disc cells to in situ genetic modification.
The success of protein and gene therapy requires the presence of an adequate number of responding cells. Disc degeneration is accompanied by a decline in cellularity. Restoring cell numbers could be achieved by either stimulating the division and inhibiting the death of endogenous cells or by introducing new cells into the disc. The latter strategy may be more successful, especially if the endogenous cells of a degenerating disc are unresponsive or otherwise abnormal. When pursuing this strategy, there are several important reasons why it is better to introduce progenitor cells than to attempt to harvest and reintroduce mature disc cells. Progenitor cells of the mesenchymal lineage, available from bone marrow, fat, and other convenient sources, could be useful. However, although the presumption exists that these types of cells can differentiate into disc cells, this has never been demonstrated. One impediment to confirming differentiation into a disc cell is our inability to identify these cells; there are no robust molecular, biochemical, or biologic markers. The serious study of disc-cell biology at this level would be most rewarding.
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