Manipulating the glial scar: chondroitinase ABC as a therapy for spinal cord injury.
Chondroitin sulphate proteoglycans (CSPGs) are potent inhibitors of growth in the adult CNS. Use of the enzyme chondroitinase ABC (ChABC) as a strategy to reduce CSPG inhibition in experimental models of spinal cord injury has led to observations of a remarkable capacity for repair. Here we review the evidence that treatment with ChABC, either as an individual therapy or in combination with other strategies, can have multiple beneficial effects on promoting repair following spinal cord injury. These include promoting regeneration of injured axons, plasticity of uninjured pathways and neuroprotection of injured projection neurons. More importantly, ChABC therapy has been demonstrated to promote significant recovery of function to spinal injured animals. Thus, there is robust pre-clinical evidence demonstrating beneficial effects of ChABC treatment following spinal cord injury. Furthermore, these effects have been replicated in a number of different injury models, with independent confirmation by different laboratories, providing an important validation of ChABC as a promising therapeutic strategy. We discuss putative mechanisms underlying ChABC-mediated repair as well as potential issues and considerations in translating ChABC treatment into a clinical therapy for spinal cord injury.
Bradbury
Elizabeth J
EJ
King's College London, Neurorestoration Group, Wolfson Centre for Age-Related Diseases, Guy's Campus, London, United Kingdom. elizabeth.bradbury@kcl.ac.uk
Carter
Lucy M
LM
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D019765:Chondroitin ABC Lyase / Q000627:therapeutic use*; D006801:Humans; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009457:Neuroglia / Q000473:pathology*; D013119:Spinal Cord Injuries / Q000188:drug therapy* / Q000473:pathology*
D019765:Chondroitin ABC Lyase