Large-Scale Chondroitin Sulfate Proteoglycan Digestion with Chondroitinase Gene Therapy Leads to Reduced Pathology and Modulates Macrophage Phenotype following Spinal Cord Contusion Injury

Chondroitin sulfate proteoglycans (CSPGs) inhibit repair following spinal cord injury. The researchers used a modified chondroitinase ABC (ChABC) delivered via lentiviral vector (LV-ChABC) to digest CSPGs and promote spinal cord repair. The study demonstrated reduced secondary injury pathology in rats treated with LV-ChABC after spinal contusion, including reduced cavitation and enhanced preservation of neurons and axons. LV-ChABC treatment altered macrophage phenotype to favor alternatively activated M2 macrophages, which are associated with tissue remodeling and repair.

• 1
  LV-ChABC treatment significantly reduced cavitation and enhanced the preservation of spinal neurons and axons at 12 weeks post-injury, compared with control-treated animals.
• 2
  LV-ChABC treatment increased the expression of the phagocytic macrophage marker CD68 early after injury, followed by increased CD206 expression at 2 weeks, suggesting a shift towards M2 macrophage polarization.
• 3
  LV-ChABC treatment promoted remodeling of specific CSPGs, enhanced vascularity, improved sensorimotor function, increased neuronal survival, reduced apoptosis, improved axonal conduction, and increased serotonergic innervation.