TAK-242 treatment and its effect on mechanical properties and gene expression associated with IVD degeneration in SPARC-null mice

Engineered extracellular vesicle-based gene therapy for the treatment of discogenic back pain

“…Few studies have characterized the effect of biologics on the biomechanical properties of the IVD given the scale, sensitivity, and feasibility of the methods. In contrast to our data, when examining the systemic effects of Toll-like receptor 4 inhibitor on the regeneration of the degenerate IVDs in a SPARC null mouse model, no changes in mechanical properties were observed [ 60 ]. This may be a result of the direct (IVD injection) versus indirect (intraperitoneal) method of drug delivery to the IVD or IVD injury versus spontaneous genetic SPARC null model [ 60 ].…”

“…In contrast to our data, when examining the systemic effects of Toll-like receptor 4 inhibitor on the regeneration of the degenerate IVDs in a SPARC null mouse model, no changes in mechanical properties were observed [ 60 ]. This may be a result of the direct (IVD injection) versus indirect (intraperitoneal) method of drug delivery to the IVD or IVD injury versus spontaneous genetic SPARC null model [ 60 ]. Thus, as validated using multiple imaging, histological, mechanical, and biochemical parameters, our findings demonstrate that FOXF1 eEVs have the potential to restore the structure and function of the injured mouse IVD to control levels in vivo highlighting the rigor and impact of our novel non-viral gene delivery strategy.…”

Roles of organokines in intervertebral disc homeostasis and degeneration

“…Additionally, these mice demonstrate a diminished lumbar neutral zone, increased spinal stiffness, and reduced spinal mobility ( 100 ). SPARC knockout results in elevated levels of inflammatory mediators and vascular endothelial growth factor, which can be mitigated by interventions like exercise and treatment with TAK-242 (a TLR-4 antagonist) or reparixin (an inhibitor of CXC chemokine receptors [CXCR1/2]) ( 80 , 101 – 103 ). Therefore, SPARC is a promising target for preventing IVDD in modulating cell–matrix interactions and governing neural, immune, and inflammatory pathways ( 79 , 104 , 105 ).…”