Combination treatment with chondroitinase ABC in spinal cord injury—breaking the barrier

Neurosci Bull, 2013 · DOI: 10.1007/s12264-013-1359-2 · Published: August 1, 2013

Spinal Cord Injury Pharmacology Regenerative Medicine

Simple Explanation

Spinal cord injuries present challenges such as tissue loss and an inhibitory environment. A promising approach involves combining treatments to address different aspects of the problem. Chondroitinase ABC (ChABC) can be a valuable component in such combinations because its mechanism of action complements other treatment strategies. ChABC degrades chondroitin sulfate proteoglycans, which form a regeneration barrier in the glial scar. By removing this barrier and increasing plasticity, ChABC creates a more favorable environment for nerve regeneration and functional recovery after spinal cord injury. This review discusses studies combining ChABC with other treatments like cell implantation, growth factors, myelin-inhibitory molecule blockers, and ion channel expression in rat spinal cord injury models, exploring ways to optimize these combination protocols for better outcomes.

Study Duration

Not specified

Participants

Rat SCI models

Evidence Level

Review

Key Findings

1
Combinatorial therapies with ChABC have shown synergistic effects with cell implantation in enhancing functional recovery after spinal cord injury, improving graft integration and axon regeneration across the lesion.
2
Combining ChABC with neurotrophins and neural progenitor cells leads to improved differentiation, migration, and integration of precursor cells, along with increased plasticity of the corticospinal tract and serotonergic axons.
3
The combination of α-Nogo-A, ChABC and rehabilitation was more effective; after treatment and 3 months of training, the combination group recovered to 80% of the level before the lesion.

Research Summary

After spinal cord injury (SCi), re-establishing functional circuitry in the damaged central nervous system (CNS) faces multiple challenges including lost tissue volume, insufficient intrinsic growth capacity of adult neurons, and the inhibitory environment in the damaged CNS. Degradation of the chondroitin sulfate proteoglycans with the chondroitinase ABC (ChABC) enzyme removes a regeneration barrier from the glial scar and increases plasticity in the CNS by removing perineuronal nets. To date, combinational therapies with ChABC have shown synergistic effects with several other strategies in enhancing functional recovery after SCi. These combinatorial approaches can now be developed for clinical application.

Practical Implications

Enhanced Functional Recovery

Combination therapies involving ChABC can lead to synergistic improvements in functional recovery after spinal cord injury compared to single treatments.

Clinical Translation Potential

The successful outcomes of combinational approaches in animal models suggest that these strategies can be further developed for clinical application in spinal cord injury patients.

Optimized Treatment Paradigms

Careful consideration of lesion models, readouts, and timing of interventions (medical, rehabilitation) is crucial for designing effective combinational treatment strategies.

Study Limitations

1
Variability in SCi lesion models and their anatomical and behavioral readouts.
2
Combinational studies are major undertakings.
3
The outcome of studies depends greatly on the animal model used.

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