What is the role of biologic therapies for symptomatic intervertebral discs in the treatment of cervical disc disease?

Updated: Apr 16, 2020
  • Author: Michael B Furman, MD, MS; Chief Editor: Dean H Hommer, MD  more...
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Answer

Biologic therapies for symptomatic intervertebral discs offer a novel approach to treatment. By effectively targeting the primary pain generator (ie, the intervertebral cervical disc) clinicians may treat the source of the pain and not just the sequelae of the degenerative cascade (ie, radiculopathy or discogenic pain). These treatments may also offer alternatives to conservative or surgical measures. Because these agents can be injected with contrast-enhanced fluoroscopic guidance, they may result in reduced morbidity to the patient.

To date several biologic compounds are under clinical and laboratory investigations. These include:

  • Growth factors, including tumor growth factor (TGF)-beta, bone morphogenetic proteins (BMP)-2, BMP -7, BMP-14: Infusion of growth factors has been shown in animal models to cause an anabolic response with increases in disc height and proteoglycan synthesis. BMP-7 and BMP-14 are currently in phase I clinical trials.

  • Gene transfer: The gene encoding the growth factor or therapeutic protein would be implanted into the disc to produce the protein in situ. Preliminary results have been promising, showing increased proteoglycan synthesis when injected into human disc cells in vitro. [51]

  • Cell therapy, including autologous disc cells, articular chondrocytes, and mesenchymal stem cells: These substances can be transplanted into vertebral discs, slowing disc degeneration. Several in vivo animal studies have shown that mesenchymal stem cells slow the progression of disc degeneration as well as regenerate the matrix. [52] Numerous other studies have demonstrated the ability of injected cells to survive, differentiate toward disc cells, and produce matrix components, including collagen II and proteoglycans. [51, 52]

  • Tissue engineering: Therapeutic agents, when injected into the intervertebral disc function to alter both biochemical and biomechanical stressors. At this time, a US Food and Drug Administration (FDA)-approved trial is underway evaluating the efficacy and safety of a fibrin sealant derived from human plasma derivatives (fibrinogen and thrombin). This substance (fibrinogen and thrombin) has been shown in animal studies to inhibit nucleus pulposus fibrosis, promote recovery of proteoglycan content, and facilitate repair of the annulus. A pilot study showed reduction in pain and disability at 1 and 2 years after a single injection. [53, 54]

In the early stage of disc degeneration, protein factors such as growth factors and proteinase inhibitors may be effective. In the intermediate stage of degeneration, cell or gene therapy may be required. In the advanced stages of disc degeneration, tissue engineering approaches will be needed.

Biologic substances offer a great potential for therapy of the degenerative disc. There have been numerous studies indicating in vitro and in vivo success in rebuilding or repairing the structure of the intervertebral disc. With these rapid advancements, these interventions may soon be available in clinical practice. What remains to be answered is if these biomechanical and biochemical alterations will offer clinically relevant findings. Whether structural changes to the disc will lead to decreased pain and increased function of the patient is unclear.


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