Sustained delivery of thermostabilized chABC enhances axonal sprouting and functional recovery after spinal cord injury

PNAS, 2010 · DOI: 10.1073/pnas.0905437106 · Published: February 23, 2010

Simple Explanation

Spinal cord injuries often lead to the formation of glial scars, which contain molecules called chondroitin sulfate proteoglycans (CSPGs) that inhibit nerve regrowth. The enzyme chondroitinase ABC (chABC) can break down these CSPGs, but it is not stable at body temperature. This study developed a method to make chABC more stable by adding a sugar called trehalose. This thermostabilized chABC was then delivered locally using a special system of hydrogels and microtubes. The results showed that the thermostabilized chABC remained active for several weeks, reduced CSPG levels, and promoted nerve growth and functional recovery in rats with spinal cord injuries, especially when combined with neurotrophin-3.

Study Duration

2 weeks and 45 days

Participants

Adult male Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
Trehalose significantly enhances the thermal stability of chABC, allowing it to remain active at 37 °C for up to 4 weeks in vitro.
2
Sustained delivery of thermostabilized chABC via a hydrogel-microtube system effectively digests CSPGs in vivo for at least 6 weeks post-SCI.
3
Combined delivery of thermostabilized chABC and neurotrophin-3 (NT-3) significantly improves locomotor function and promotes axonal sprouting after spinal cord injury.

Research Summary

This study addresses the challenge of delivering chABC, an enzyme that promotes nerve regeneration after spinal cord injury, by thermostabilizing it with trehalose and using a hydrogel-microtube system for sustained local delivery. The thermostabilized chABC (TS-chABC) maintains its enzymatic activity for an extended period, effectively digests CSPGs at the injury site, and enhances axonal sprouting. Combining TS-chABC with neurotrophin-3 (NT-3) further improves locomotor function, suggesting a promising therapeutic approach for spinal cord injury.

Practical Implications

Minimally Invasive Therapy

The sustained delivery system avoids the need for chronically implanted catheters and pumps, offering a less invasive therapeutic option.

Combination Therapy Potential

The delivery system enables the combination of chABC with other therapeutic agents like neurotrophic factors, potentially enhancing treatment efficacy.

Overcoming Regenerative Failure

By effectively digesting CSPGs and promoting axonal sprouting, this approach addresses a major impediment to nerve regeneration after spinal cord injury.

Study Limitations

1
Diffusion of chABC in human spinal cord tissue needs further investigation.
2
Long-term effects and potential side effects of chABC-induced plasticity require further study.
3
The hemisection injury model used may not fully represent the complexities of all spinal cord injuries.

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