Sialidase enhances recovery from spinal cord contusion injury

PNAS, 2010 · DOI: 10.1073/pnas.1006683107 · Published: June 22, 2010

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

The injured spinal cord does not readily allow axons to regrow, which limits recovery after injury. Myelin-associated glycoprotein (MAG) is one of the inhibitors that prevents regeneration. MAG binds to sialoglycans on axons, inhibiting their growth. The enzyme sialidase can remove sialic acids, breaking the MAG-sialoglycan bond and potentially allowing axons to regrow. In this study, rats with spinal cord injuries were treated with sialidase. The treatment improved motor function, autonomic reflexes, and axon sprouting, suggesting that sialidase could be a therapy for spinal cord injuries.

Study Duration

5 weeks

Participants

Sprague-Dawley rats (230–250 g)

Evidence Level

Not specified

Key Findings

1
Sialidase treatment significantly enhanced hindlimb motor function in rats with spinal cord contusion injuries, as measured by the BBB locomotor rating scale.
2
Sialidase treatment improved autonomic function, specifically enhancing the range of renal sympathetic nerve activity (RSNA) responsiveness to changes in blood pressure.
3
Sialidase treatment increased the density of serotonergic axons caudal to the spinal cord injury site, suggesting enhanced axon sprouting.

Research Summary

This study investigated the effect of sialidase on recovery from spinal cord contusion injury in rats. Sialidase was delivered intrathecally to the injury site for two weeks, and motor behavior, autonomic physiology, and anatomic outcomes were assessed three weeks later. The results showed that sialidase treatment significantly enhanced hindlimb motor function, improved autonomic reflexes, and increased axon sprouting compared to the control group. Sialidase effectively cleaved sialic acid residues from spinal cord sialoglycans. The findings suggest that sialoglycans are potential therapeutic targets for spinal cord injury and that sialidase is a candidate therapy. The study establishes the feasibility of producing and delivering sialidase to the contused spinal cord, and its potential for therapeutic benefit.

Practical Implications

Therapeutic Potential

Sialidase could be a potential therapeutic agent for spinal cord injury by promoting axon regeneration and improving motor and autonomic function.

Target Validation

The study validates sialoglycans as therapeutic targets for spinal cord injury, suggesting that modifying sialoglycan interactions could promote recovery.

Drug Development

The enzyme used in these studies, V. cholerae sialidase, has advantages as a potential biological drug, as it is produced at high concentration, readily purified, and remarkably stable.

Study Limitations

1
The number of animals in the study was limited.
2
Motor improvement with sialidase treatment was variable.
3
Additional studies are required to identify which sialidase substrates and/or products are most responsible for improved functional recovery.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury