Abstract: Spinal cord injuries have overwhelming physical and occupational implications for patients. Moreover, the extensive and long-term medical care required for spinal cord injury significantly increases healthcare costs and resources, adding a substantial burden to the healthcare system and patients’ families. In this context, chondroitinase ABC, a bacterial enzyme isolated from Proteus vulgaris that is modified to facilitate expression and secretion in mammals, has emerged as a promising therapeutic agent. It works by degrading chondroitin sulfate proteoglycans, cleaving the glycosaminoglycanchains of chondroitin sulfate proteoglycans into soluble disaccharides or tetrasaccharides. Chondroitin sulfate proteoglycans are potent axon growth inhibitors and principal constituents of the extracellular matrix surrounding glial and neuronal cells attached to glycosaminoglycan chains. Chondroitinase ABC has been shown to play an effective role in promoting recovery from acute and chronic spinal cord injury by improving axonal regeneration and sprouting, enhancing the plasticity of perineuronal nets, inhibiting neuronal apoptosis, and modulating immune responses in various animal models. In this review, we introduce the classification and pathological mechanisms of spinal cord injury and discuss the pathophysiological role of chondroitin sulfate proteoglycans in spinal cord injury. We also highlight research advancements in spinal cord injury treatment strategies, with a focus on chondroitinase ABC, and illustrate how improvements in chondroitinase ABC stability, enzymatic activity, and delivery methods have enhanced injured spinal cord repair. Furthermore, we emphasize that combination treatment with chondroitinase ABC further enhances therapeutic efficacy. This review aimed to provide a comprehensive understanding of the current trends and future directions of chondroitinase ABC -based spinal cord injury therapies, with an emphasis on how modern technologies are accelerating the optimization of chondroitinase ABC development.

Key words: axonal regeneration, chondroitin sulfate proteoglycans, chondroitinase ABC, combination treatments, delivery methods, enzymatic activity, glycosaminoglycan chains, spinal cord injury, stability