Feasible stabilization of chondroitinase abc enables reduced astrogliosis in a chronic model of spinal cord injury

CNS Neurosci Ther, 2019 · DOI: 10.1111/cns.12984 · Published: January 1, 2019

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

Spinal cord injury (SCI) often results in a glial scar containing molecules like chondroitin sulfate proteoglycans (CSPGs). Chondroitinase ABC (ChABC) can degrade CSPGs, potentially improving SCI outcomes, but it's thermally unstable. This study shows that using a sucrose solution can stabilize ChABC, reducing glial scarring and slightly improving locomotor recovery in rats with chronic SCI.

Study Duration

6 weeks

Participants

15 adult Sprague-Dawley rats

Evidence Level

Not specified

Key Findings

1
A 2.5 mol/L sucrose solution best stabilized ChABC activity in vitro for up to 14 days.
2
ChABC in a sucrose solution reduced reactive gliosis at the injury site in rats with chronic spinal cord injury.
3
Rats treated with ChABC in sucrose showed slightly enhanced locomotor recovery.

Research Summary

This study aimed to find a feasible strategy to preserve ChABC catalytic activity using stabilizing agents. The study demonstrated that a 2.5 mol/L sucrose solution best stabilized ChABC as far as 14 days in vitro and improved activity in conditions mimicking in vivo usage. A single intraspinal treatment with ChABC and sucrose reduced reactive gliosis and slightly enhanced locomotor recovery in rats with chronic SCI, suggesting a feasible strategy to ameliorate ChABC-based treatments.

Practical Implications

Clinical Translation

The use of sucrose solutions may offer a more feasible and less invasive approach to stabilize ChABC for treating spinal cord injuries, potentially improving clinical outcomes.

Combinatorial Therapy

Combining sucrose-stabilized ChABC injections with rehabilitation could enhance axonal regeneration and locomotor recovery compared to ChABC alone.

Drug Delivery

The findings suggest that simple sugar solutions can be effective stabilizers for labile enzymes like ChABC, improving their therapeutic potential.

Study Limitations

1
The study requires better insights about the stabilization mechanism exerted by sucrose.
2
A deep characterization of sucrose effects on the tissues surrounding injection site is mandatory before bringing this approach to clinics
3
Longer observational timeframes may be required to asses any potential incremental functional recovery and nervous regeneration.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury