Chondroitinase ABC Enzyme: A Potential Treatment Option for Spinal Cord Injury

After spinal cord injury (SCI), axons fail to regenerate in the adult mammalian central nervous system (CNS) leading to permanent paralysis.[1] At the site of injury, glial reaction occurs resulting in the formation of glial scar. Glial reaction results in recruitment of microglia, oligodendrocytes precursors, meningeal cells, astrocytes, and stem cells, besides containing oligodendrocytes and myelin debris. Most of these cells release molecules, inhibitory to axon regeneration, resulting in failure of regeneration. Even remyelination may be unsuccessful in such an environment.[2] Glial scar also contains chondroitin sulfate proteoglycan (CSPG), which along with inflammation, is recovery inhibiting factor.[3]

Treatment strategy targeting CSPG using chondroitinase ABC (ChABC) enzyme offers the opportunity to improve the outcome of SCI. ChABC is obtained from Proteus vulgaris and it acts by degrading the glycosaminoglycan side chains of CSPGs.[4] Degradation of CSPG with the use of ChABC removes a regeneration inhibition from the glial scar. The plasticity in the CNS is increased with the removal of perineural nets. The mechanism of action of ChABC is unique and does not overlap with mechanisms of other available treatment options for SCI, thus making ChABC an attractive option for the treatment of SCI in combination with other strategies.[5]

Treatment with ChABC has shown promising results in animal models of SCI. In a study in male Wistar rats using combination of low-level laser therapy (LLLT) as anti-inflammatory agent and ChABC as CSPG digesting factor after inducing SCI by “clip compression,” combination of LLLT and ChABC showed more effect on reduction of cavity size, improvement of myelination and number of axons around the cavity and decreasing the expression of glycogen synthase kinase-3 β, CSPG and aquaporin 4 expression compared to LLLT and ChABC alone, resulting in more functional recovery in combination group.[3] In another experiment, ChABC treatment reinstated postsynaptic activity below the lesion as evident to electrical stimulation of corticospinal neurons and promoted functional recovery of locomotor and proprioceptive behaviors in rats.[1] ChABC has also shown to promote functional recovery in acute SCI in rats when used in combination with rehabilitation, even after 4 weeks of spinal injury.[6]

In a recently concluded study with dog models of naturally occurring severe chronic spinal cord injuries, intraspinal injections of ChABC have shown favorable results and authors have recommended to start human trials.[7]

Although no human trials have been conducted till date, the results in animal studies are promising and points toward the potential benefit of ChABC in SCI.