Soluble Nogo-Receptor-Fc decoy (AXER-204) for neural repair in patients with chronic cervical spinal cord injury: a first-in-human and randomized clinical trial

Lancet Neurol, 2023 · DOI: 10.1016/S1474-4422(23)00215-6 · Published: August 1, 2023

Spinal Cord Injury Neurorehabilitation Research Methodology & Design

Simple Explanation

Spinal cord injuries disrupt connections in the nervous system, leading to lasting neurological problems. This study explored whether a drug called AXER-204 could help repair these connections and improve recovery. AXER-204 works by blocking substances that prevent nerve growth, potentially allowing damaged nerves to regrow or form new connections. The trial involved two parts: an initial safety test and a randomized, placebo-controlled comparison. While the overall study didn't show a significant improvement, a closer look at certain patients suggested that AXER-204 might be helpful for those with incomplete spinal cord injuries who hadn't previously received the drug.

Study Duration

104 days (Part 2 repeat dose)

Participants

24 participants in part 1, 27 participants in part 2, adults with chronic (>1 year) cervical traumatic SCI

Evidence Level

Level 1, Randomized, double-blind, placebo-controlled trial

Key Findings

1
AXER-204 was found to be safe and well-tolerated in patients with chronic cervical SCI at the doses tested.
2
The drug reached targeted concentrations in the cerebrospinal fluid (CSF), indicating it was able to access the spinal cord.
3
Post hoc analysis suggested clinically meaningful benefit of AXER-204 in treatment-naïve patients with neurologically incomplete SCI.

Research Summary

This study delivers the first, to our knowledge, clinical trial of a rationally designed pharmacological treatment for neural repair in chronic SCI. AXER-204 appeared safe and reached targeted CSF concentrations with exploratory biomarkers consistent with target engagement and synaptic stabilization. Post hoc analyses indicate a need for future efficacy trials in moderate severity SCI patients without prior AXER-204 exposure.

Practical Implications

Future Trials Needed

Further research is warranted to evaluate the effectiveness of AXER-204 in specific subgroups of SCI patients, particularly those with incomplete injuries.

Broader Applications

The observed safety profile of AXER-204 suggests potential utility in other neurological conditions where neural repair and plasticity are desired, such as stroke or multiple sclerosis.

Biomarker Discovery

The study identified changes in CSF synaptic adhesion proteins, which may serve as potential biomarkers for assessing treatment response in future SCI trials.

Study Limitations

1
Wide range of injury severity may have obscured potential benefits in specific subgroups.
2
Dual participation of some patients in parts 1 and 2 complicated efficacy analysis.
3
Pharmacokinetic and proteomic results are from single dose analyses.

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