Clinical stage anti-RGMa monoclonal antibody elezanumab promotes bladder recovery and neuroplasticity after traumatic spinal cord injury

Spinal cord injury (SCI) causes severe and often permanent neurological deficits, including neurogenic lower urinary tract dysfunction. Although restoration of bladder function is a major clinical priority after SCI and would profoundly improve care and quality of life, it remains underrepresented in neurotrauma research. Central to this pathology is Repulsive Guidance Molecule a (RGMa), a potent inhibitor of axonal outgrowth and neuronal differentiation that is upregulated following central nervous system injury. In this study, we evaluated the therapeutic efficacy of elezanumab, a human anti-RGMa monoclonal antibody tested in clinical trial for acute SCI, on bladder function in a clinically relevant bilateral impact-compression model of traumatic thoracic SCI in female rats. Quantitative urodynamic and cystometric analyses demonstrated that elezanumab administered initially at 3 h post-SCI and then weekly for 6 weeks significantly reduced urinary retention, reflex bladder activity, and intravesical pressure in SCI rats. Morphological assessment revealed that RGMa neutralization limited pathological bladder hypertrophy, with reductions in bladder mass correlating with reduced urine retention. Neuroanatomical mapping via retrograde tracing, together with exploratory transsynaptic tracing, was consistent with increased supraspinal connectivity in pathways involved in micturition. Moreover, elezanumab promoted axonal plasticity of descending catecholaminergic and serotonergic fibers within the lumbosacral spinal cord. These structural changes were associated with reduced bladder pressure and improved neurological recovery. Together, these findings suggest that RGMa inhibition via elezanumab promotes recovery within key components of the micturition circuitry following traumatic SCI.