Compounds co-targeting kinases in axon regulatory pathways promote regeneration and behavioral recovery after spinal cord injury in mice

Exp Neurol, 2022 · DOI: 10.1016/j.expneurol.2022.114117 · Published: September 1, 2022

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

Recovery from spinal cord injury is limited by the inability of damaged nerve fibers (axons) to regrow in the central nervous system. A new therapeutic strategy targets multiple kinases involved in both external and internal regulation of axon growth. The kinase inhibitor RO48 promotes axon growth in vitro and in vivo, leading to improved behavioral recovery in mice after spinal cord injury.

Study Duration

Not specified

Participants

Mice

Evidence Level

Not specified

Key Findings

1
RO48 promotes neurite growth from various neuronal types in vitro, including hippocampal, cortical, sensory, and human iPSC-derived glutamatergic neurons.
2
In multiple mouse models of spinal cord injury, RO48 promotes corticospinal tract (CST) sprouting and/or regeneration.
3
In a cervical dorsal hemisection model, RO48 improves behavioral recovery in rotarod, gridwalk, and pellet retrieval tasks.

Research Summary

This study investigates a therapeutic strategy co-targeting kinases involved in extrinsic and intrinsic regulatory pathways to promote axon regeneration after spinal cord injury (SCI). The kinase inhibitor RO48 promotes neurite growth from various neuronal types in vitro and corticospinal tract (CST) sprouting and/or regeneration in multiple mouse models of SCI. RO48 improves behavioral recovery in a cervical dorsal hemisection model, suggesting its potential application as a therapeutic strategy for SCI and related neurological disorders.

Practical Implications

Therapeutic Potential

RO48 shows promise as a therapeutic for spinal cord injury, promoting axon growth and functional recovery.

Polypharmacology Strategy

Co-targeting multiple kinases may be a more effective strategy for promoting axon regeneration than targeting a single pathway.

Broad Applicability

RO48's effectiveness across different neuronal types and injury models suggests broad applicability for CNS injuries.

Study Limitations

1
The study primarily focuses on preclinical mouse models, and further research is needed to translate these findings to humans.
2
The precise mechanisms by which RO48 promotes axon regeneration and behavioral recovery need further elucidation.
3
The long-term effects and potential side effects of RO48 treatment were not extensively investigated.

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