RGMa inhibition with human monoclonal antibodies promotes regeneration, plasticity and repair, and attenuates neuropathic pain after spinal cord injury

Scientific Reports, 2017 · DOI: 10.1038/s41598-017-10987-7 · Published: August 17, 2017

Spinal Cord Injury Pain Management Regenerative Medicine & Stem Cells

Simple Explanation

Traumatic spinal cord injury (SCI) leads to cell death, axonal damage, and increased inhibitory molecules, hindering regeneration and recovery. Repulsive guidance molecule A (RGMa) inhibits neurite growth. The study found RGMa is markedly upregulated after SCI in rats and humans. Blocking RGMa with human monoclonal antibodies improved motor function, neuronal survival, axonal regeneration, and reduced neuropathic pain in rats after SCI.

Study Duration

9 weeks

Participants

63 adult female Wistar rats

Evidence Level

Not specified

Key Findings

1
RGMa is significantly upregulated in multiple cell types following impact-compression SCI in rats and in the injured human spinal cord.
2
Systemic administration of human anti-RGMa monoclonal antibodies improved motor function and gait in rats after SCI.
3
RGMa blocking antibodies promoted neuronal survival, enhanced plasticity of serotonergic pathways and corticospinal tract axonal regeneration, and attenuated neuropathic pain.

Research Summary

This study investigates the therapeutic potential of human anti-RGMa antibodies in treating spinal cord injury (SCI) by promoting regeneration and reducing neuropathic pain. The research demonstrates that RGMa is upregulated after SCI in both rats and humans, and blocking RGMa with human antibodies improves functional recovery in rats. The findings suggest that RGMa inhibition promotes neuronal survival, axonal regeneration, and attenuates neuropathic pain, highlighting the therapeutic benefit of RGMa-specific antibodies for SCI.

Practical Implications

Clinical Translation

The use of human monoclonal antibodies that can be administered systemically provides a clinically relevant approach for treating SCI.

Therapeutic Target

RGMa is identified as a key therapeutic target for promoting both neuroprotection and regeneration after SCI.

Pain Management

RGMa inhibition represents a potential strategy for attenuating neuropathic pain associated with SCI.

Study Limitations

1
Study conducted on rats, further research needed for human application
2
The long-term effects of RGMa inhibition are not fully explored
3
The specific mechanisms underlying neuropathic pain reduction require further investigation

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