Restoration of Motor Function through Delayed Intraspinal Delivery of Human IL-10-Encoding Nucleoside-Modified mRNA after Spinal Cord Injury

Research, 2023 · DOI: 10.34133/research.0056 · Published: March 9, 2023

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

This study explores a new approach to treating spinal cord injuries using messenger RNA (mRNA) to deliver an anti-inflammatory protein called interleukin-10 (IL-10) directly to the injured spinal cord. The mRNA is modified and packaged into lipid nanoparticles (LNPs) to protect it and help it enter cells in the spinal cord. The goal is to reduce inflammation and promote recovery. The results showed that this treatment reduced inflammation, protected nerve cells, and improved motor function in rats with spinal cord injuries, suggesting a promising new therapy.

Study Duration

9 weeks

Participants

203 Sprague-Dawley female rats

Evidence Level

Not specified

Key Findings

1
Intraspinal delivery of hIL-10 mRNA-LNP significantly decreased the densities of CD68-, Iba-1-, and GSA-B4-positive cells compared with the injured spinal cords of SCI and mRNA-GFP animals at all examined time points.
2
mRNA-LNP-induced hIL-10 treatment results in a delayed expression of potent neuromodulatory factors such as tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) and ciliary neurotrophic factor (CNTF) in the affected spinal segments.
3
hIL-10 mRNA treatment proved to be effective at inducing significant morphological and functional recovery of the injured spinal cord tissue in rats, with functional improvement nonsignificantly greater compared to rats treated with hIL-10 protein delivered by an osmotic pump.

Research Summary

This study investigated the use of nucleoside-modified mRNA encoding human interleukin-10 (hIL-10) delivered via lipid nanoparticles (LNPs) to treat spinal cord injury (SCI) in rats. The intraspinal administration of hIL-10 mRNA-LNP led to reduced microglia/macrophage reaction, increased expression of tissue inhibitor of matrix metalloproteinase 1 (TIMP-1) and ciliary neurotrophic factor (CNTF), and significant functional recovery compared to controls. The results suggest that nucleoside-modified mRNAs encoding neuroprotective factors represent an effective strategy for spinal cord injury repair, offering a potential alternative to traditional protein delivery methods.

Practical Implications

Therapeutic Potential

mRNA-based therapy could provide a safer and more controllable method for delivering therapeutic proteins to the injured spinal cord, potentially improving outcomes for individuals with SCI.

Reduced Inflammation

The study's findings suggest that hIL-10 mRNA-LNP can effectively modulate the inflammatory response following SCI, promoting a more favorable microenvironment for tissue repair and regeneration.

Improved Functional Recovery

The observed improvements in locomotor function and morphological restoration indicate that this approach could lead to enhanced functional outcomes for individuals with SCI.

Study Limitations

1
The study was conducted in a rat model, and further research is needed to determine the efficacy and safety of this approach in humans.
2
The long-term effects of hIL-10 mRNA-LNP treatment on spinal cord repair and functional recovery were not fully elucidated in this study.
3
Further studies are needed to optimize the dosage, timing, and delivery method of mRNA-LNP for SCI treatment.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury