J Korean Orthop Assoc.  2024 Oct;59(5):335-341. 10.4055/jkoa.2024.59.5.335.

Current Biological Therapies and Clinical Trials for Lumbar Degenerative Disc Disease

Affiliations
  • 1Department of Orthopedic Surgery, SMG-SNU Boramae Medical Center, Seoul National University College of Medicine, Seoul, Korea

Abstract

Conventional treatments for degenerative disc disease have limitations in regenerating the intervertebral disc because of its anatomical characteristics. Hence, researchers are investigating biological therapies for degenerative disc disease. The advances in genetic engineering and fields, such as tissue engineering, are accelerating the development of biological treatments for degenerative discs. Biological treatments for degenerative discs focus on inhibiting cell apoptosis and maintaining cell populations within the disc. Current biological therapies studied include gene therapy, cell therapy, and growth factor therapy. Gene therapy involves the use of RiboNucleic Acid (RNA) interference, such as small interfering RNA (siRNA), to inhibit genes related to cell apoptosis and to explore therapeutic targets. Cell therapy, which involves a direct injection of stem cells into the disc, has attracted considerable attention. Mesenchymal stem cells and notochordal cells are commonly used, with mesenchymal stromal/stem cells (MSCs) being preferred because of their ease of production and anti-inflammatory effects. Several clinical trials using MSCs have reported favorable clinical outcomes, such as alleviating lower back pain, but disc height was not restored. These results were not from randomized trials, and double-blind clinical trials using MSCs are currently underway. Research is ongoing to promote anabolic processes within the nucleus pulposus by injecting growth factors into the disc. Preclinical studies have shown that a biglycan fragment targeting transforming growth factor (TGF)-β can inhibit degenerative changes in the disc, and clinical trials using growth/differentiation factor (GDF)-5 are currently in progress. Research on biological treatments for degenerative discs is being conducted in three main areas: gene therapy, cell-based therapy, and growth factor-based therapy. Although cell therapy using MSCs has shown symptomatic improvement in clinical trials, a double-blind clinical trial is still needed to confirm the therapeutic effects.

Keyword

degenerative disc disease; disc regeneration; mesenchymal stem cell; gene therapy; growth factor
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