Development of Neural Repair Therapy for Chronic Spinal Cord Trauma: Soluble Nogo Receptor Decoy from Discovery to Clinical Trial

Curr Opin Neurol, 2023 · DOI: 10.1097/WCO.0000000000001205 · Published: December 1, 2023

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

After a spinal cord injury, the connections between surviving neurons are disrupted, leading to persistent neurological problems. Currently, there are no medical treatments available to help repair these connections. This review discusses the development of AXER-204, a therapy aimed at repairing neural connections, from its initial testing in animals to its recent clinical trial for individuals with chronic spinal cord injury. Studies suggest that blocking the Nogo-66 Receptor 1 (NgR1) pathway can promote the repair of neural connections. A clinical trial of AXER-204, which targets this pathway, showed promising signs, suggesting it could be beneficial for certain patients with incomplete spinal cord injuries.

Study Duration

Not specified

Participants

Participants with chronic cervical SCI

Evidence Level

Level 1, Randomized controlled clinical trial

Key Findings

1
The soluble receptor decoy AXER-204 was safe and well-tolerated in a first-in-human clinical trial for chronic cervical SCI.
2
Across all participants in the clinical trial, upper extremity strength did not improve with AXER-204 treatment.
3
Post-hoc and biomarker analyses suggest that AXER-204 may benefit treatment-naïve patients with incomplete SCI in the chronic stage.

Research Summary

NgR1 signaling restricts neurological recovery in animal studies of CNS injury. The recent clinical trial of AXER-204 provides encouraging signals supporting future focused trials of this neural repair therapeutic. AXER-204 studies provide a roadmap for the development of additional and synergistic therapies for chronic SCI.

Practical Implications

Future Clinical Trials

Future clinical trials should focus on treatment-naïve individuals with incomplete SCI to assess the efficacy of AXER-204.

Combination Therapies

AXER-204 could be combined with rehabilitative training or other interventions like acute intermittent hypoxia or neuromodulation to enhance its benefits.

Biomarker Research

Further studies should investigate the role of AXER-204 in synaptic adhesion protein metabolism to understand its effects on neuroplasticity.

Study Limitations

1
The clinical trial included participants with both complete and incomplete SCI, which may have limited the overall capacity for repair.
2
A portion of participants had previously received AXER-204 in an earlier phase of the trial, potentially creating a ceiling effect for subsequent benefit.
3
The study did not include rehabilitative training, which could have enhanced the effects of AXER-204.

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