NASS 2025 RECAP
Degenerative Disc Disease Therapies: Contemporary Practice and Future Directions
Roberto Acosta-Gómez, MD
Spine Surgery Department Hospital General de México México City, México
Degenerative disc disease remains a leading cause of disability worldwide and continues to challenge clinicians, researchers, and health systems due to its complex and multifactorial nature. These challenges were highlighted at the NASS 2026 Annual Meeting in Denver during the session titled, “Intervertebral Disc Therapies: Voodoo or the Future?” with presentations by Gregory K. Paschal, MS, Andres Bonilla, PhD, Harvey Smith, MD, and Ira L. Fedder, MD, explored emerging biologic and interventional strategies for disc degeneration.
Genetic predisposition, mechanical loading, inflammatory cascades, and age-related metabolic changes interact to drive a progressive decline in disc structure and function.1-3 Traditionally, treatment strategies focused primarily on symptom relief through analgesics, physical therapy, rehabilitation and reserving surgical interventions such as discectomy, disc replacement, or spinal fusion for advanced stages of disease.1,2
However, the intervertebral disc can’t be understood only as a mechanical spacer between two vertebrae. Intervertebral disc is a highly specialized tissue with its own biology, complex biomechanical behavior and a very limited capacity for adaptation due to its poor vascular supply. With advancing degeneration, the intradiscal environment undergoes profound biological changes, including reduced oxygen availability, acidification, compromised nutrient transport, progressive cell depletion, degradation of the extracellular matrix, and a gradual loss of functional capacity.3,4
Recognition of these interrelated processes has prompted a paradigm shift in treatment philosophy, moving toward therapeutic strategies designed to preserve, regulate, or reestablish disc biology, rather than relying solely on mechanical compensation.
Many of the advances in this field have been enabled by translational research, particularly through preclinical models that allow controlled evaluation of degenerative mechanisms and therapeutic responses. Spontaneous degeneration in large animals, such as sheep, offers a valuable opportunity to study age-related and region-specific disc failure that closely resembles human pathology.5 These models have revealed important biological differences between cervical and lumbar intervertebral discs and have supported proteomic and transcriptomic analyses identifying differential expression of regulatory proteins such as SPARC and ASPORIN, which play a role in extracellular matrix turnover and disc homeostasis.5
Induced experimental models, including annular disruption and needle puncture techniques, continue to play an essential role by providing controlled and reproducible systems for evaluating biomechanical behavior, biomaterials, and novel biologic interventions.1 At the same time, functional outcome measures such as gait analysis, facial expression-based pain scoring, and artificial intelligence supported pain assessment are increasingly incorporated to better capture clinically meaningful endpoints beyond structural imaging, thereby strengthening translational relevance.4
Andres Bonilla, PhD
Among currently available biologic interventions, platelet rich plasma has gained widespread clinical adoption. Prospective clinical studies have demonstrated consistent improvements in pain and functional outcomes following intradiscal PRP injection, with sustained benefit reported for up to five years in selected patient populations.6,7
The proposed mechanisms of action include modulation of intradiscal inflammation, activation of anabolic cellular pathways, and support of extracellular matrix maintenance. However, variability in preparation protocols and dosing regimens remains an important limitation when interpreting clinical outcomes.6-8 Owing to its autologous origin and favorable safety profile, PRP represents a reasonable therapeutic option for patients with mild to moderate degenerative disc disease who are not candidates for operative management.
Bone marrow derived mesenchymal stem cells constitute another relevant therapeutic strategy in the management of degenerative disc disease. Early phase clinical trials have demonstrated meaningful reductions in pain and disability scores, accompanied by preservation of disc height and improvement in disc hydration parameters.8,9 Despite these encouraging findings, the intradiscal microenvironment remains a significant barrier to sustained efficacy, as low pH, hypoxic conditions, and restricted nutrient diffusion adversely affect cell viability and long-term survival.3
In response to these challenges, increasing attention has been directed toward the use of biologic carriers, including hyaluronic acid, fibrin, and collagen-based scaffolds, which may improve cellular retention, provide transient structural support, and limit the risk of cell migration or ectopic differentiation.10,13
One of the most notable advances in this area has been the development of standardized allogeneic cell-based therapies. Discogenic progenitor cells obtained from human nucleus pulposus tissue have shown reproducible clinical benefit in dose escalation trials, with sustained improvements in pain, functional outcomes, and disc related structural parameters reported at follow up periods of up to two years.11
Gregory K. Paschal, MS
In a similar context, rexlemestrocel-L, which combines mesenchymal precursor cells with hyaluronic acid, is currently being evaluated in phase three clinical trials using clinically meaningful endpoints, including reductions in opioid use and improvements in health related quality of life.10 Collectively, these approaches illustrate the progression of the field toward regulated biologic therapies manufactured under pharmaceutical standards, representing a clear departure from earlier experimental and heterogeneous interventions.
Pharmacologic innovation continues to expand the therapeutic options for degenerative disc disease. Molecular strategies targeting inflammatory signaling pathways, including NF KB decoy oligodeoxynucleotides, are designed to inhibit catabolic gene expression and modulate intradiscal inflammation at the cellular level.14 In parallel, bioactive agents such as melatonin, resveratrol, and metformin have shown potential to mitigate oxidative stress, suppress pro inflammatory cytokine activity, and promote cellular resilience within the disc environment.3,13
Although many of these therapies remain in preclinical development or early phase clinical investigation, their emergence highlights an increasing emphasis on disease modifying approaches that move beyond symptomatic analgesia to address the biological mechanisms underlying disc degeneration.
Progress in bioengineering has advanced in parallel with these biologic strategies. Allogeneic nucleus pulposus grafts, including VIA Disc NP, have demonstrated encouraging clinical and biomechanical outcomes by improving disc hydration and restoring load bearing properties through matrices that closely approximate native extracellular matrix composition.12
In a similar manner, injectable hydrogel systems designed to reestablish nucleus pressurization, together with annular scaffold technologies intended to reinforce the annulus fibrosus and reduce the risk of reherniation, represent complementary approaches to functional disc restoration that build upon established principles of disc biology and biomechanics.1,3,13 Collectively, these technologies aim not only to alleviate symptoms but also to preserve or reconstruct disc integrity, with the potential to delay or reduce progression toward more invasive surgical interventions.12
Integration of biological and biomechanical principles has therefore become central to contemporary therapeutic strategies. Degenerative disc disease results in simultaneous disruption of viscoelastic behavior, nutrient transport, extracellular matrix organization, and structural stability.1,3 Consequently, effective treatment paradigms must address multiple dimensions of degeneration rather than rely on isolated mechanisms.
The most promising approaches are likely to involve combined strategies incorporating cellular therapies, targeted pharmacologic modulation, and biomechanical support, delivered through optimized carriers or scaffolds that enhance cellular survival and localized therapeutic effect.8,11,13 This multidimensional framework reflects a growing consensus that meaningful disc regeneration requires coordinated and synergistic intervention rather than single modality treatment.
Harvey Smith, MD
Despite these advances, patient selection remains a critical limitation to the successful application of regenerative therapies. Available evidence indicates that biologic and regenerative interventions are most effective in patients with early to intermediate stages of disc degeneration, in whom residual cellular populations and extracellular matrix architecture remain responsive to modulation.8,9
With advancing disease, reduced vascular supply, endplate dysfunction, and substantial structural deterioration significantly diminish the potential for durable biological repair. These considerations underscore the need for improved biomarkers and functional outcome measures to facilitate earlier and more accurate patient selection, as well as for rigorous late phase clinical trials to establish the efficacy of emerging disc biologics and support widespread clinical adoption.
Furthermore, the speakers emphasized that new disc biologics typically will need two Phase III trials to prove efficacy and obtain widespread adoption.
The treatment paradigm for degenerative disc disease is undergoing a fundamental shift. Regenerative and interventional strategies are evolving from conceptual approaches into clinically relevant therapies that directly address the biological mechanisms underlying disc degeneration, rather than focusing solely on its structural end-stage manifestations. Future advances will likely depend on integrated treatment frameworks that combine cellular therapies, biomaterials, targeted pharmacologic modulation, and biomechanical restoration. Sustained commitment to translational research, interdisciplinary collaboration, and the development of standardized outcome measures will be critical to refining these strategies and defining their appropriate clinical application.
While we are still learning about how long some of these newer disc treatments last and which patients benefit the most, current evidence shows that treatment is moving beyond just controlling pain. We now have options that aim to protect the disc, reduce inflammation, and in some cases support its function, which represents an important step forward in how we manage disc degeneration.
References
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- Smith LJ, Nerurkar NL, Choi KS, Harfe BD, Elliott DM. Degeneration and regeneration of the intervertebral disc: lessons from development. Dis Model Mech. 2011;36(21):31-41.
- Vo NV, Hartman RA, Patil PR, et al. Molecular mechanisms of biological aging in intervertebral discs. J Orthop Res. 2013;31(8):1186-1193.
- Liang C, Li H, Tao Y, et al. Responses of nucleus pulposus cells to mechanical loading: implications for intervertebral disc degeneration. Bone Res. 2021;9:7.
- Humbert L, Bonilla A, Smith HE, et al. Transcriptomic characterization of healthy and degenerated ovine intervertebral disc cells. bioRxiv. Published online Nov 6, 2025.
- Tuakli-Wosornu YA, Terry A, Boachie-Adjei K, et al. Lumbar intradiscal platelet-rich plasma injections: a prospective, double-blind, randomized controlled study. PMR. 2016;8(1):1-10.
- Akeda K, Ohishi K, Takegami N, et al. Intradiscal injection of autologous platelet-rich plasma releasate to treat discogenic low back pain: a preliminary clinical trial. Medicina (Kaunas). 2022;58(6):734.
- Muthu S, Jeyaraman M, Chellamuthu G, Khanna M, Rajasekaran S. Current evidence on regenerative therapies for lumbar disc degeneration: a systematic review. Glob Spine J. 2022;12(6):1248-1262.
- Noriega DC, Ardura F, Hernández-Ramajo R, et al. Intervertebral disc repair by allogeneic mesenchymal bone marrow cells: a randomized controlled trial. Transplantation. 2017;101(8):1945-1951.
- Amirdelfan K, Bae H, McJunkin T, et al. Allogeneic mesenchymal precursor cells for chronic low back pain associated with degenerative disc disease: a randomized controlled trial. Spine. 2021;46(22):1503-1512.
- Gornet MF, Burkus JK, Shaffrey CI, et al. Discogenic cell therapy for lumbar disc degeneration: two-year clinical outcomes. Spine J. 2021;21(4):607-619.
- Beall DP, Davis TT, Amirdelfan K, et al. Supplemental nucleus pulposus allograft in patients with lumbar discogenic pain: results of a prospective feasibility study. BMC Musculoskelet Disord. 2025;26:437.
- Xie L, Huang W, Fang Z, et al. Biological regulation of intervertebral disc degeneration by mesenchymal stem cells: perspectives on therapeutic mechanisms. Front Bioeng Biotechnol. 2020;8:7.
- Kato T, Iwasaki M, Sudo H, et al. NF-κB decoy oligodeoxynucleotide inhibits intervertebral disc degeneration in a rabbit model. Spine. 2020;45(13):E789-E798.