AAV Vector Mediated Delivery of NG2 Function Neutralizing Antibody and Neurotrophin NT-3 Improves Synaptic Transmission, Locomotion, and Urinary Tract Function after Spinal Cord Contusion Injury in Adult Rats

The Journal of Neuroscience, 2023 · DOI: https://doi.org/10.1523/JNEUROSCI.1276-22.2023 · Published: March 1, 2023

Simple Explanation

This study explores a novel gene therapy approach to improve recovery after spinal cord injury in rats. The therapy involves delivering an antibody that neutralizes the inhibitory functions of a molecule called NG2, combined with a neurotrophin called NT-3. The results showed improvements in locomotion, bladder function, and nerve transmission in the treated rats, suggesting a potential therapeutic strategy for spinal cord injury.

Study Duration

9 weeks

Participants

Adult female Sprague Dawley rats

Evidence Level

Not specified

Key Findings

1
AAV-NG2Ab and AAV-NT3 treatment improved locomotor function after contusion SCI.
2
Treatment with AAV-NG2Ab1AAV-NT3 improved bladder function after contusion SCI.
3
Treatment with AAV-NG2Ab and AAV-NT3 improved transmission to lumbar motoneurons in chronically contused rats.

Research Summary

This study demonstrates the beneficial effects of AAV-mediated transduction with NG2Ab for neutralization of inhibitory function of NG2 proteoglycan, combined with AAV-mediated transduction with neurotrophin NT3, on the recovery of function after contusion SCI. Best improvements of both locomotor and bladder functions were seen in the group that received combined AAV-NG2Ab and AAV-NT3 treatments. These beneficial effects of combined treatment on recovery of function after SCI associated with improved anatomic plasticity, synaptic transmission, and axonal excitability.

Practical Implications

Therapeutic Target Identification

NG2 proteoglycan represents a potential therapeutic target for interventions aimed at improving recovery after spinal cord injury.

Combined Therapies

Combining NG2 neutralization with neurotrophic support may offer synergistic benefits for promoting functional recovery.

Clinical Translation

The AAV-mediated gene therapy approach warrants further investigation for potential clinical translation in human spinal cord injury patients.

Study Limitations

1
The study was conducted on adult female rats, and the results may not be directly applicable to other populations.
2
The study focused on a specific type of spinal cord injury (contusion) and the findings may not generalize to other injury mechanisms.
3
Long-term effects of AAV-mediated gene therapy were not examined.

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