Disc Degeneration Research Articles

The role of loading-induced convection versus diffusion on the transport of small molecules into the intervertebral disc.

Limited nutrient transport is hypothesized to be involved in intervertebral disc (IVD) degeneration. It is widely recognized that the dominant mode of transport of small molecules such as glucose is via diffusion, rather than convection. However, recent findings suggest a role for convection-induced by fast (motion-related) and slow (diurnal) dynamic loading in molecular transport of even such small solutes. The aim of this study was to investigate whether fluid exchange induced by simulated physiological loading (composed of both fast cyclic or slower diurnal loading) can influence the molecular transport of a small molecule through the cartilage endplate (CEP) into the nucleus pulposus (NP) of IVDs. The molecular transport of fluorescein through the CEP and into the NP was studied in a bovine CEP/NP explant model and loading was applied by an axial compression bioreactor. The loaded explants (convection and diffusion) were compared to unloaded explants (diffusion alone). In the initial 24h, there were no differences between loaded and unloaded explants, indicating that convection did not enhance molecular transport of small solutes over diffusion alone. Notably, after 48h which corresponds to two complete diurnal cycles of tissue compression, fluid exudation/imbibing and redistribution, the fluorescein concentration was significantly increased in the top and bottom layer of the explant, when compared to the unloaded explant. Slower diurnal cyclic compression of the IVD might enhance the transport of small molecules into the IVD although it could not be discerned whether this was due to diffusion/convection or a combination.

Machine learning-based analysis of programmed cell death types and key genes in intervertebral disc degeneration.

Intervertebral disc degeneration (IVDD) is intricately associated with various forms of programmed cell death (PCD). Identifying key PCD types and associated genes is essential for understanding the molecular mechanisms underlying IVDD and discovering potential therapeutic targets. This study aimed to elucidate core PCD types, related genes, and potential drug interactions in IVDD using comprehensive bioinformatic and experimental approaches. Using datasets GSE167199, GSE176205, GSE34095, GSE56081, and GSE70362, relevant gene expression and clinical data were analyzed. Differential expression gene (DEG) analysis identified upregulated genes linked to 15 PCD types. Gene Set Variation Analysis (GSVA) was employed to pinpoint key PCD types contributing to disc degeneration. Core genes were identified through machine learning techniques, while immune infiltration and single-cell analysis helped identify apoptosis-related cell types. Molecular docking, along with in vivo and in vitro experiments using a murine IVDD model, validated potential drug interactions. The results identified apoptosis, autophagy, ferroptosis, and necroptosis as key PCD types in IVDD. A gene module associated with apoptosis showed a strong correlation with the severity of disc degeneration, revealing 34 central genes in the gene network. Drug screening identified Glibenclamide as effectively interacting with PDCD6 and UBE2K. Subsequent in vitro and in vivo experiments demonstrated that Glibenclamide reduced apoptosis and delayed disc degeneration progression. This study provides a comprehensive bioinformatics analysis of PCD in IVDD, identifying four primary PCD types contributing to the disease's progression. The findings offer novel insights into the molecular pathology of disc degeneration and suggest promising therapeutic strategies for future treatment development.

Delayed percutaneous intradiscal hydrogel herniation causing neurological injury after minor trauma: illustrative case.

Percutaneous intradiscal hydrogel injection has been used to treat low-back pain (LBP) due to degenerative disc disease with or without mild radicular pain. Complications from these procedures are underreported. In this case lesson, the authors present a rare case of a patient with herniated intradiscal hydrogel following a minor trauma leading to neurological injury. A 36-year-old female who had been previously treated with L4-5 and L5-S1 intradiscal hydrogel injections for LBP presented with painful, progressive right-sided lower-extremity weakness after experiencing a twisting trauma. Cross-sectional imaging results revealed a herniated hydrogel-based disc implant in the spinal canal. She underwent an urgent L4-5 laminectomy for decompression and removal of the herniated implant. A large annular defect was noted. Postoperatively, she had resolution of her right leg pain but experienced persistent right foot drop requiring an ankle-foot orthosis. Herniated intradiscal hydrogel implants can lead to permanent neurological injury. While the risk factors for hydrogel herniation have not been elucidated, they can be related to pre-existing disruptions to the annulus and/or posterior longitudinal ligament, excess volume of hydrogel injection, and insufficient fixation time. Further research is needed to determine the safety and efficacy of this technology. https://thejns.org/doi/10.3171/CASE24394.

Network Pharmacology and In Vivo Experimental Verification of the Mechanism of the Qing'e Pill for Treating Intervertebral Disc Degeneration.

The Qing'e Pill (QEP) is widely used to alleviate low back pain and sciatica caused by Intervertebral Disc Degeneration (IDD). However, its active components, key targets, and molecular mechanisms are not fully understood. The aim of this study is to elucidate the molecular mechanisms through which the QEP improves IDD using database mining techniques. Active components and candidate targets of the QEP were identified using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform and the Bioinformatics Analysis Tool for Molecular Mechanisms of Traditional Chinese Medicine. IDD-related targets were obtained from the GeneCards database, and liver- and kidney-specific genes were retrieved from the BioGPS database. The intersection of these candidate targets was analyzed to identify potential targets for the QEP in IDD. A protein-protein interaction network analysis was performed using STRING and Cytoscape 3.7.2 software. Core targets were further analyzed through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to assess the binding affinity of active components to candidate targets, and animal experiments were conducted for validation. We identified 65 potentially active components of the QEP that corresponded to 1,093 candidate targets, 2,108 IDD-related targets, and 1,113 liver- and kidney-specific genes. Key components included quercetin, berberine, isorhamnetin, and emodin. The primary candidate targets were Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3. The GO and KEGG analyses revealed the involvement of these targets in Wnt signaling, TNF signaling, Wnt receptor activation, Frizzled binding, and Wnt-protein interactions. Molecular docking showed strong binding between these components and their targets. Animal experiments demonstrated that the QEP treatment significantly reduced the expression of Wnt5A, CTNNB1, IL-1β, MAPK14, MMP9, and MMP3 at high, medium, and low doses compared with the model group. The QEP alleviated IDD by modulating the Wnt/MAPK/MMP signaling pathways and reducing the release and activation of key factors.

Self-healing hydrogels loaded with Spatholobi Caulis alleviate disc degeneration by promoting autophagy in nucelus pulposus

Intervertebral disc degeneration (IDD) is a common degenerative disease of the spine that has a significant impact on both society and human health. Many studies have confirmed that there is a close relationship between IDD and senescence and apoptosis, and autophagy can combat apoptosis and senescence. Spatholobi caulis (SC) is an herb that contains various active compounds that are effective in tissue repair and regeneration, but it has not been explored in field of IDD. In this study, it was first found that SC can boost autophagy and reduce the apoptosis and senescence of Nucleus pulposus cell (NPCs). However, our animal studies revealed limited absorption of SC. To improve the bioavailability and efficacy of SC, we developed a hydrogel incorporating quaternary ammonium chitosan (QCS) and oxidized starch (OST) as carriers for SC. The QCS-OST/SC hydrogel exhibits excellent compatibility with cells, can be easily injected, and can release SC durably. At the cellular level, the QCS-OST/SC hydrogel enhances cell viability, initiates autophagy and release of the extracellular matrix (ECM), and inhibits cellular senescence and apoptosis. The injection of the QCS-OST/SC hydrogel via microneedles (MNs) into discs had successfully diminished disc degeneration in rats, which shows that this hydrogel has broad potential in the treatment of IDD.

Evaluation of Lumbar Spine on MRI in Young Adults presenting with Chronic Backaches

Objective: This study aimed to establish a correlation between clinical symptoms and MRI findings in individuals with chronic back pain. Methodology: This Descriptive cross-sectional study was conducted over a period of four months after ethical approval in the Radiology department at a Tertiary Care Hospital in Lahore. Acohort of 135 young adults were assessed through a consecutive sampling method and underwent lumbar spine MRI examinations. Results: The pool of participants in the study encompassed 42.2% males and 57.8% females, aged between 18 and 40 years, with an average age of 31.5 years and a standard deviation of 6.06. There were four prominent MRI findings: Lumbar Spondylosis (46%, Disc Degeneration (25%, Disc Bulge (10%), and Disc Desiccation (9%). The study also found significant correlations between these findings and clinical characteristics, with Lumbar Spondylosis linked to lower limb numbness and mobility difficulties, and Disc Bulge correlated with pain duration. Conclusion: The findings underscore the effectiveness of MRI scans in identifying underlying causes of chronic back pain in young adults in Pakistan. Keywords: Lumber spondylosis, disc degeneration, disc bulge, Lower Limb Numbness, and Magnetic Resonance Imagin

YAP1 exacerbates pyroptosis and senescence in nucleus pulposus cells by promoting BNIP3-mediated mitophagy

Yes-associated protein 1 (YAP1) is a crucial downstream effector of the Hippo pathway that plays a role in regulating inflammation and mitochondrial function. However, whether YAP1 regulates pyroptosis in nucleus pulposus (NP) cells caused by inflammation via mitophagy remains unclear. This study aimed to investigate the effects of YAP1 on the pyroptosis of NP cells induced by LPS. Here, we demonstrated that the protein expression of YAP1 in the NP tissue of degenerative discs was significantly reduced. Next, we found that NLRP3 inflammasome activation in YAP1-overexpressing (YAP1-ov) NP cells was further enhanced in the LPS-induced inflammatory microenvironment. YAP1-ov strongly aggravated inflammation-induced pyroptosis and senescence, but these effects were reversed by the inhibition of BNIP3-mediated mitophagy. However, comparative analysis of the overexpression of YAP1 in normal discs and discs after annulus fibrosus puncture revealed that YAP1-ov accelerated the degeneration of normal discs and attenuated the degeneration of annulus fibrosus punctured discs in vivo. Additionally, YAP1-ov upregulated the expression of TNFAIP3, an anti-inflammatory protective protein, and CLPP, a vital protein in the mitochondrial unfolded protein response, in NP cells. Collectively, the above results revealed that YAP1 exacerbates LPS-induced pyroptosis and senescence of NP cells by promoting BNIP3-mediated mitophagy, which causes disc degeneration. Notably, YAP1-ov mitigated the degeneration of the disc caused by annular needle puncture in vivo, suggesting its potential as a therapeutic candidate foracute IDD injury.

Oxygen-controllable injectable hydrogel alleviates intervertebral disc degeneration by balancing extracellular matrix metabolism

Nucleus pulposus (NP) cells, situated at the core of intervertebral discs, have acclimated to a hypoxic environment, orchestrating the equilibrium of extracellular matrix metabolism (ECM) under the regulatory influence of hypoxia inducible factor-1α (HIF-1α). Neovascularization and increased oxygen content pose a threat, triggering ECM degradation and intervertebral disc degeneration (IVDD). To address this, our study devised an oxygen-controllable strategy, introducing laccase into an injectable and ultrasound-responsive gelatin/agarose hydrogel. Laccase-mediated reactions were employed to deplete oxygen, establishing a hypoxic microenvironment that upregulated HIF-1α expression. The activation of hypoxia-inducible factors significantly enhanced the expression of aggrecan and collagen II, concurrently suppressing Matrix metalloproteinases (MMP13) and A Disintegrin and Metalloproteinase with Thrombospondin motifs (ADAMTS5) levels, thereby restoring the equilibrium of ECM metabolism. Simultaneously, the hydrogel facilitated the recruitment of stem cells into the NP through the controlled release of ATI2341, activating C-X-C chemokine receptor type 4 (CXCR4). Moreover, ultrasound amplification enhanced ATI2341 release, promoting the migration of NP stem cells. The hydrogel's efficacy in mitigating metabolic imbalances and inhibiting IVDD progression was substantiated in a rat puncture IVDD model through hydrogel injection into the discs. In conclusion, this hypoxia-inducible hydrogel, responsive to thermal stimuli from ultrasound, presents a promising avenue for IVDD treatment.

The effects of extracellular matrix-degrading enzymes polymorphisms on intervertebral disc degeneration.

The objective of the current study was to investigate the correlation between polymorphisms in extracellular matrix-degrading enzymes and the risk of intervertebral disc degeneration (IDD) diseases. The databases PubMed, Embase, and Cochrane Database were systematically queried from the inception until March 2023 to ascertain studies that meet the eligibility criteria. Utilizing a standardized data collection form to extract data from individual studies. The data were quantified using odds ratio (OR) along with its corresponding 95% confidence interval (95% CI), following an allelic model of inheritance. The study included a total of nine studies and indicated that the presence of rs17576 in the MMP9 gene was significantly associated with an increased risk of IDD diseases (GG: 1.30, 95% CI [1.09-1.55], p = 0.004). The presence of other polymorphisms in extracellular matrix-degrading enzymes did not exhibit a significant association with the susceptibility to IDD. The current study demonstrated a noteworthy correlation between the GG genotype of MMP-9 rs17576 and susceptibility to IDD. The available evidence is insufficient to substantiate the correlation between other extracellular matrix-degrading enzymes and susceptibility to IDD. The constraints of this analysis necessitate further research involving larger sample sizes across diverse ethnicities to provide a comprehensive understanding of the true impact of these polymorphisms on susceptibility to IDD.

The Role of Immunocyte Infiltration Regulatory Network Based on hdWGCNA and Single-Cell Bioinformatics Analysis in Intervertebral Disc Degeneration.

Immune infiltration plays a crucial role in intervertebral disc degeneration (IDD). In this study, we explored the immune microenvironment of IDD through single-cell bioinformatics analysis. Three single-cell datasets were integrated into this study. Nucleus pulposus cells (NPCs) were divided into subgroups based on characteristic genes, and the role of each subgroup in the IDD process was analyzed through pseudo-time trajectory analysis. The hub genes were obtained using hdWGCNA, further identified by bulk datasets and pseudo-time sequence. The expression of the hub genes defined the NPCs related to immune infiltration, and the interaction between these NPCs and immunocytes was explored. The NPCs were divided into four subgroups: reserve NPCs, HCL-NPCs, response NPCs, and support NPCs, which, respectively, dominate the four processes of IDD: non, mild, moderate, and severe degeneration. SPP1 and ICAM1 were identified as the nucleus pulposus immune infiltration hub genes. Macrophages and myelocytes played pro-inflammatory roles in the SPP1-ICAM both-up NPC group through the SPP1-CD44 pathway and ICAM1-ITGB2 ligand-receptor pathway, respectively. At the same time, both-up NPCs sought self-help inflammation remission from neutrophils through the ANXA1-FPR1 pathway. The systematic analysis of the differentiation and immune infiltration landscapes helps to understand IDD's overall development process. Our data suggest that SPP1 and ICAM1 may be new targets for the treatment of inflammatory infiltration in IDD.

Assessing MRI Scans of Spinal Disc Degeneration Using Machine Learning

Abstract: Chronic back pain caused by degenerative changes in the spinal disc has significantly impacted the quality of life of patients. Magnetic resonance imaging gives a very clear visualization of the intervertebral disc; however, it is still subjective and more mentally demanding when it is a manual assessment. Therefore, the present paper discusses the possibility of integrating image processing techniques with machine learning algorithms in order to arrive at more accurate diagnosis for spinal disc degeneration. Preprocessing the image, segmentation, and feature extraction are incorporated along with various machine learning models like convolutional neural networks (CNN) and support vector machines (SVM) into the review of present methodologies. Our results show that these hybrid approaches improve classification accuracy and aid in early detection for better management of the patient. This project helps in identifying the four stages of spinal disc degeneration.

Curculigoside upregulates BMAL1 to decrease nucleus pulposus cell apoptosis by inhibiting the JAK/STAT3 pathway

BackgroundIntervertebral disc degeneration (IVDD) is a natural process that occurs with aging and is the main cause of low back pain (LBP). Basic helix-loop-helix ARNT-like 1 (BMAL1) plays key roles in the pathogenesis of many diseases. The present study investigates the role of curculigoside (CUR), which has been reported to be a potential anti-apoptotic compound in other diseases. MethodsDysregulated genes were identified by RNA sequencing (RNA-seq). Western blotting (WB), immunohistochemistry (IHC), immunofluorescence (IF) staining, and real-time fluorescent quantitative PCR were used to detect BMAL1 expression in 25 human intervertebral disc (IVD) specimens (male: female =13:12), tissues from BMAL1-knockout mice and from an IVDD mouse model. The regulatory effects of CUR and BMAL1 in NP cells after siRNA transfection were examined by flow cytometry, IF staining and WB. The therapeutic effect of intraperitoneal CUR injection was also evaluated in mice. ResultsBMAL1 expression was negatively correlated with IVDD severity and was significantly lower in degenerative NP cells. After BMAL1 knockdown using siRNA, the apoptosis rate of degenerative NP cells was significantly higher, while transfection with a lentivirus overexpressing BMAL1 exerted the opposite effect. Bioinformatics analysis revealed that BMAL1 is regulated by the JAK-STAT3 pathway, and CUR upregulated BMAL1 expression by inhibiting STAT3 phosphorylation, subsequently alleviating NP cell apoptosis and increasing extracellular matrix (ECM) components., thus alleviating IVDD. ConclusionsCUR can inhibit apoptosis and improve the ECM by upregulating BMAL1 expression, which is reduced in IVDD. This study provides a therapeutic strategy to alleviate apoptosis associated with inflammation-induced IVDD.

The clinical results and function of the intersegmental disc after posterior-only partial corpectomy for lumbar burst fractures.

We treated the burst spinal fracture with posterior subtotal corpectomy and reconstruction. In some cases, the endplate and the adjacent disc can be preserved during the operation. The adjacent disc retained its mobility after the removal of the posterior pedicle screws. This study evaluated the clinical results and function of the intersegmental caudal disc after the removal of posterior pedicle screws for lumbar burst fractures. The study analyzed retrospectively 36 patients with acute burst traumatic lumbar fractures who underwent posterior partial subtotal corpectomy and reconstruction with preservation of the inferior endplate of the fractured vertebral body and the adjacent caudal disc, and sequential removal of the posterior pedicle screw 1 year after the second surgery from March 2015 to December 2021. All patients were followed for approximately 1 year after pedicle screw removal. Demographic data, anterior vertebral body height, local kyphosis, motion, caudal disc degeneration, and clinical outcomes were evaluated. After removal of the posterior pedicle screws, the intersegmental disc retained a range of motion of 10.55 ± 5.58°, and the disc degeneration was graded by Pfirrmann criteria from 2.21 ± 1.15 before first surgery to 3.18 ± 1.46 at last follow-up after second surgery. There were 2 cases of superficial wound infection, and 5 cases of postoperative neuralgia recovering after 3 months. Anterior fusion was achieved, although postoperative subsidence of the mesh was observed in 6 cases and screw loosening in 9 cases. Posterior-only partial subtotal corpectomy with preservation of the adjacent caudal disc not only achieved a good clinical effect, but also preserved intersegmental caudal disc function after removal of posterior pedicle screws approximately 1 year later. This technique is a promising alternative for cases in which the endplate obviates injury.

Lumbar disc herniation

The most common cause of disc herniation is the degeneration of the intervertebral disc. Consequently, lumbar disc herniations are amongst the most common pathologies of the lumbar spine. Factors that can increase the risk of disc herniation include genetics, weight, occupational risk factors, smoking, as well as apredominantly sedentary profession. Pathognomonic symptoms of aherniated disc include sciatica, caused by the compression of one or more spinal nerve roots. The clinical sequelae of lumbar disc herniations range from mild low back and buttock pain to severe, immobilising cases of sciatica to cauda equina compression syndromes. In 1-1.5% of cases, acauda equina syndrome may occur. This cauda equina syndrome may be considered an emergency situation that requires immediate attention and surgical decompression. The same applies to significant and rapidly deteriorating neurological deficits (< 24 h). In all other cases, which represents the majority of all patients,substantial pain relief can be achieved with nonsurgical measures. If an adequate and intolerable pain relief cannot be achieved despite intense conservative treatment measures after an extended period of 6-12weeks, surgical removal of the disc herniation may be indicated. Lumbar disc herniations may be addressed surgically with minimally invasive techniques. The goal of the surgery is full and sufficient safe removal of the herniated disc fragments in order to decompress the spinal nerves as well as the cauda equina. The two most commonly used surgical techniques (endoscopic/microsurgical) entail fivedifferent approaches (endoscopic: interlaminar, transforaminal; microsurgical: interlaminar, translaminar, extraforaminal). Patients are generally fully mobilized within hours after the surgery without any further restrictions. Postoperative rehabilitation measures are often carried out, but have no scientifically proven influence on the outcome of the operation. This article sheds light on the diagnostic and therapeutic procedures, techniques and special features of this socio-medically very important clinical picture.

Identification of KCNQ1 as a diagnostic biomarker related to endoplasmic reticulum stress for intervertebral disc degeneration based on machine learning and experimental evidence.

Intervertebral disc degeneration (IDD) is a primary cause of low back pain and disability. Cellular senescence and apoptosis due to endoplasmic reticulum stress (ERS) are key in IDD pathology. Identifying biomarkers linked to ERS in IDD is crucial for diagnosis and treatment. We utilized machine learning on gene expression profiles from the Gene Expression Omnibus database to discover biomarkers associated with ERS in IDD. Gene set enrichment analysis (GSEA) and single-sample GSEA were applied to evaluate the immunological features and biological functions of these biomarkers. The expression of KCNQ1 was experimentally validated. Machine learning identified KCNQ1 as a diagnostic biomarker for ERS in IDD, confirmed by Western blotting. GSEA indicated that KCNQ1 influences IDD primarily through the Notch signaling pathway and by regulating macrophage and monocyte infiltration. KCNQ1, identified as an ERS-associated biomarker in IDD, impacts the Notch signaling pathway and immune cell infiltration, suggesting its potential as a therapeutic target for IDD. Further validation through prospective studies and additional experimental methods is necessary to elucidate the role of KCNQ1 in IDD comprehensively.

Comparison of Disc Degeneration between Pyogenic Spondylitis and Noninfected Lumbar Spondylosis: A Multicenter Retrospective Study with Propensity Score Matching

Comparison of Disc Degeneration between Pyogenic Spondylitis and Noninfected Lumbar Spondylosis: A Multicenter Retrospective Study with Propensity Score Matching

Efficacy of Anterior Cervical Discectomy and Fusion Versus Cervical Disc Arthroplasty in the Treatment of Cervical Degenerative Disc Disease, Radiculopathy, and Myelopathy: A Systematic Review.

Cervical degenerative disc disease (DDD) is a condition in which the discs in the neck deteriorate, causing symptoms including neck and arm pain, muscle weakness, and incoordination. In severe cases, it can lead to nerve and spinal cord compression, resulting in radiculopathy and myelopathy. This review aimed to assess the effectiveness of two surgical treatments, anterior cervical discectomy and fusion (ACDF) and cervical disc arthroplasty (CDA), for addressing cervical DDD, radiculopathy, and myelopathy. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a literature search was conducted in the PubMed and BioMed Central databases, from January to March 2024. Thirty-one studies were included, comparing the outcomes of ACDF and CDA in patients with cervical DDD, radiculopathy, and myelopathy. Data were analyzed to evaluate outcomes such as the Neck Disability Index (NDI), pain levels, neurological status, incidence of secondary surgeries, range of motion (ROM) maintenance, and occurrence of adjacent segment disease. CDA demonstrated comparable or superior clinical success to ACDF. Both the techniques showed similar improvements in NDI, pain levels, and neurological status during medium- and long-term follow-ups. CDA had lower rates of secondary surgeries and adverse events related to surgery or implants compared to ACDF. It also demonstrated a lower incidence of adjacent segment disease and better ROM preservation. The evidence supports CDA as a safe and effective alternative to ACDF for patients with cervical DDD, particularly those who may benefit from motion preservation. However, further long-term, multicenter randomized controlled trials are needed to provide more definitive guidance for clinical practice.

FOXO3a overexpression ameliorates intervertebral disc degeneration by decreasing NLRP3-mediated pyroptosis

FOXO3a overexpression ameliorates intervertebral disc degeneration by decreasing NLRP3-mediated pyroptosis

Is Cervical Disc Degeneration a Compensatory Mechanism in Hirayama Disease? A Retrospective Case‒Control Study.

Retrospective Cohort Study. This study aimed to explore the association between cervical disc degeneration and disease progression in patients with Hirayama disease, with a particular focus on changes in the cervical intervertebral disc space height and potential compensatory mechanisms. This retrospective study included 35 patients diagnosed with Hirayama disease (HD), who were compared with 35 healthy control subjects matched for age and sex. This study focused on collecting and analyzing cervical disc grades and intervertebral space heights from C2 to C7, aiming to assess the extent of cervical disc degeneration between HD patients and the control group. The analysis used independent sample t tests and Mann‒Whitney U tests for demographic data and Spearman's correlation coefficient to explore the relationship between disc degeneration and age. Compared with the control group, patients with Hirayama disease presented significant reductions in intervertebral disc height (P < .01) and increased disc degeneration. Within the HD group, most patients displayed multisegment degeneration (30 out of 35), and more than half presented with full-segment disc degeneration (20 out of 35), which was significantly different from the normal population (P < .01). Patients with Hirayama disease exhibit disc degeneration and reduced intervertebral space height, which may represent a compensatory response.

PCRX-201, a novel IL-1Ra gene therapy treatment approach for low back pain resulting from intervertebral disc degeneration.

Low back pain is the leading cause of global disability with intervertebral disc (IVD) degeneration a major cause. However, no current treatments target the underlying pathophysiological causes. PCRX-201 presents a novel gene therapy approach that addresses this issue. PCRX-201 codes for interleukin-1 receptor antagonist, the signalling inhibitor of the pro-inflammatory cytokine interleukin-1, which orchestrates the catabolic degeneration of the IVD. Here, the ability of PCRX-201 to transduce human nucleus pulposus cells to increase IL-1Ra production was assessed together with effects on catabolic pathways. When transduced with PCRX-201, the production and release of IL-1Ra was increased in degenerate human nucleus pulposus cells and tissue. Whereas, the production of downstream proteins, including IL-1β, IL-6, MMP3, ADAMTS4 and VEGF were decreased in both cells and tissue, indicating a reduction in IL-1-induced catabolic signalling. Here, a novel gene therapy vector, PCRX-201, was shown to transduce degenerate NP cells and tissue, increasing the production of IL-1Ra. The increased IL-1Ra resulted in decreased production of catabolic cytokines, enzymes and angiogenic factors, whilst also increasing aggrecan expression. This demonstrates PCRX-201 enables the inhibition of IL-1-driven IVD degeneration. The ability of PCRX-201 to elicit anti-catabolic responses is promising and warrants further development to determine the efficacy of this exciting, novel gene therapy.