Non-viral-mediated suppression of AMIGO3 promotes disinhibited NT3-mediated regeneration of spinal cord dorsal column axons

Scientific Reports, 2018 · DOI: 10.1038/s41598-018-29124-z · Published: July 5, 2018

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This study investigates a new approach to promote the regeneration of damaged nerve fibers in the spinal cord using a non-viral gene delivery method. The researchers focused on blocking a protein called AMIGO3 and simultaneously boosting the activity of a growth factor called NT3 in nerve cells. The results showed that this combination therapy significantly improved nerve regeneration, recovery of nerve signal transmission, and overall functional recovery in rats with spinal cord injuries.

Study Duration

6 Weeks

Participants

Adult female Sprague-Dawley rats (n=12 per group)

Evidence Level

Not specified

Key Findings

1
Suppression of AMIGO3 combined with NT3 overexpression, induced DRGN to grow neurites on a CME substrate in vitro.
2
In vivo-jetPEI-delivered shAMIGO3/gfp plasmid DNA increased transduction in all sizes of DRGN and efficiently knocked down AMIGO3 while simultaneously increasing NT3 production.
3
Knockdown of AMIGO3 and simultaneous stimulation with NT3 promoted significant DRGN axon regeneration after DC injury, correlated with significant improvements in CAP amplitudes and sensory/locomotor function.

Research Summary

This study demonstrates that suppressing AMIGO3 and simultaneously stimulating with NT3 can promote the regeneration of damaged spinal cord axons. The use of a non-viral vector, in vivo-jetPEI, for gene delivery to DRGN proved effective in knocking down AMIGO3, upregulating NT3, and enhancing functional recovery. The findings suggest that targeting AMIGO3 could be a promising therapeutic strategy for promoting axon regeneration and functional recovery after spinal cord injury.

Practical Implications

Therapeutic Target

AMIGO3 represents a novel therapeutic target for promoting axon regeneration after spinal cord injury.

Non-Viral Delivery

In vivo-jetPEI offers a potentially safer and more efficient alternative to viral vectors for gene delivery in spinal cord injury treatment.

Combination Therapy

Combining AMIGO3 suppression with NT3 stimulation may enhance the efficacy of spinal cord regeneration therapies.

Study Limitations

1
The study was conducted on rats, and the results may not be directly applicable to humans.
2
The T8 DC lesion model may not fully represent the complexity of human spinal cord injuries.
3
The long-term effects of AMIGO3 suppression and NT3 stimulation were not investigated.

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