Blocking inhibitors of axon growth after spinal cord injury

Spinal cord injury can severely impair motor, sensory, bowel, bladder, and sexual functions, often with serious effects on physical and psychological outcomes. 1 Karsy M Hawryluk G Modern medical management of spinal cord injury. Curr Neurol Neurosci Rep. 2019; 19: 65 Crossref PubMed Scopus (124) Google Scholar No effective pharmacological treatments are available for spinal cord injury, and clinical studies that aim to restore neurological function are needed. Various potential therapeutic strategies are emerging, with the hope that knowledge from neuroscience research might be applied to improve patients’ quality of life. For example, in animal models of spinal cord injury, a weak imposed direct or oscillating current field can enhance regeneration of damaged axons. 2 Hamid S Hayek R Role of electrical stimulation for rehabilitation and regeneration after spinal cord injury: an overview. Eur Spine J. 2008; 17: 125-126 Crossref Scopus (157) Google Scholar However, despite promising results in animals, clinical translation is progressing slowly. Cell-based regenerative therapy is an attractive strategy for spinal cord injury because transplanted cells can provide trophic support, modulate inflammatory responses, and remyelinate denuded axons in animal models, 3 Arriola A Kiel ME Shi Y McKinnon RD Adjunctive MSCs enhance myelin formation by xenogenic oligodendrocyte precursors transplanted in the retina. Cell Res. 2010; 20: 728-731 Crossref PubMed Scopus (22) Google Scholar but challenges associated with administrated cells, including early senescence and retained epigenetic memory, need to be addressed before cellular products can be translated to the clinic. 4 Ahuja C S Nori S Tetreault L et al. Traumatic spinal cord injury-repair and regeneration. Neurosurgery. 2017; 80: S9-22 Crossref PubMed Scopus (432) Google Scholar Soluble Nogo-Receptor-Fc decoy (AXER-204) in patients with chronic cervical spinal cord injury in the USA: a first-in-human and randomised clinical trialThis study delivers the first, to our knowledge, clinical trial of a rationally designed pharmacological treatment intended to promote neural repair in chronic SCI. AXER-204 appeared safe and reached target CSF concentrations; exploratory biomarker results were consistent with target engagement and synaptic stabilisation. Post-hoc subgroup analyses suggest that future trials could investigate efficacy in patients with moderately severe SCI without prior AXER-204 exposure. Full-Text PDF