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Advances in Rehabilitation Medicine

Examining Emerging Therapies for Intervertebral Disc Degeneration

Faculty in the Department of Rehabilitation Medicine at Weill Cornell Medicine and the Department of Rehabilitation and Regenerative Medicine at Columbia University Irving Medical Center are at the forefront of investigating effective and sustainable strategies for pain management and functional improvement for intervertebral disc degeneration. In recent years, treatment options have expanded to include regenerative therapies. These newer interventions, however, come with varying levels of research into their efficacy.

“My research interests focus on regenerative medicine, an area of subspecialization that is emerging as a very promising field. But applications of regenerative and restorative therapy approaches, such as growth factors and platelet rich plasma, and other orthobiologics, require a deeper body of research to support their application to the spine,” says Jaspal R. Singh, MD, Director of Interventional Spine, Department of Rehabilitation Medicine at NewYork-Presbyterian/Weill Cornell Medical Center and Co-Director of the Weill Cornell Medicine Center for Comprehensive Spine Care.

Dr. Jaspal Singh

In a comprehensive review of research on these emerging therapies, Dr. Singh and his co-authors look at the evidence that supports their application to lumbar discogenic pain based on the factors involved in the origin of the disc disease. “It is widely accepted that disc degeneration is the consequence of an imbalance between matrix anabolism and catabolism,” notes Dr. Singh. “Therefore, the selection of treatment modalities should be based on the underlying molecular components of these competing processes.”

In their review, published in the April 2021 issue of the International Journal of Spine Surgery, the authors note that while the balance between anabolic and catabolic processes allows for multiple treatment approaches for intervertebral disc degeneration, there is also a role for disrupting the catabolic cascade to attain anticatabolic effects that promote disc regeneration and maintain homeostasis. Among the therapeutic interventions they examined are:

Protein Growth Factor: Growth differentiation factor (GDF), a member of the bone morphogenetic protein family, has been the focus on many studies as a therapeutic target for discogenic pain. GDF has been shown to be an important link between the anabolic and catabolic processes of disc degeneration, providing a balance between anabolic and catabolic processes that is central to homeostatic maintenance of the intervertebral disc. In particular, the growth factor TGF-β3 has been shown to play a role in transforming disc structure via cell differentiation.

With disc degeneration generally involving destruction of matrix components, inhibition of tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, has also been well studied in the treatment of intervertebral disc degeneration, with studies demonstrating significant and enduring pain relief. Similarly, therapy blocking the cytokine Interleukin-1 (IL-1), has helped prevent inflammatory-mediated damage to the disc. A study comparing the impact of each of these cytokines on matrix degeneration revealed that inhibition of IL-1 was more effective than inhibition of TNF-α in reducing degradation in normal or degenerated discs.

Platelet-Derived Growth Factor: Platelet-rich plasma (PRP) has become an adjunct treatment in several clinical situations due to its regenerative properties. The high concentration of growth factors and platelets found in PRP provides a regenerative stimulus that promotes healing and repair in injured tissue. PRP injections are now becoming a widely accepted therapy for musculoskeletal diseases overall and has been studied for its role in the repair of intervertebral discs. In vitro studies have had encouraging results, including demonstrating effectiveness as an anti-inflammatory agent, in stimulating cell proliferation, and for increasing proteoglycan and collagen synthesis. While clinical studies continue to evaluate intradiscal injection of PRP for degenerative disc disease, those that are available have demonstrated statistically significant improvement in outcomes measures such as the Visual Analogue Scale, Numerical Pain Rating Scale, and Oswestry Disability Index.

Prolotherapy: Prolotherapy used for pain management involves an injection of an agent such as hypertonic dextrose, phenol, or sodium morrhuate solution to create an inflammatory response to repair connective tissue. Dextrose, which is the more commonly used solution as its properties of water solubility and safe entry are well known, creates an inflammatory response to repair connective tissue. While still in the early stages of clinical evaluation, the results to date suggest that further evaluation is warranted.

“Unequivocally, finding the pain generator and the diagnosis are the most important factors before venturing into any of these treatments,” says Dr. Singh. “Regenerative medicine techniques will continue to evolve and undergo rigorous study for their role in treating intervertebral disc degeneration, and the data emerging holds great promise for the patients that seek relief from one of the world’s most widespread health problems.”

Read More

Intervertebral Disc Degeneration: The Role and Evidence for Non-Stem-Cell-Based Regenerative Therapies. Singh S, Patel AA, Singh JR. International Journal of Spine Surgery. 2021 Apr;15(s1):54-67.

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Dr. Jaspal Singh

NewYork-Presbyterian

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