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579: Anti-Nogo-A antibodies: A causal treatment for neurogenic lower urinary tract dysfunction due to spinal cord injury?

M.P. Schneider, Steffisburg (CH)
Schneider M.P. 1 , Sartori A. 1 , Ineichen B. 1 , Schwab M. 2 , Kessler T. 1
1University of Zürich, Balgrist University Hospital, Spinal Cord Injury Center & Research, Dept. of Neuro-Urology, Zürich, Switzerland, 2Brain Research Institute, University of Zürich, Dept. of Health Sciences and Technology, Zürich, Switzerland, 3
33rd Annual EAU Congress Copenhagen
Date – time - Location
18 March 2018, 14:00 - 15:30, Green Area, Room 1 (Level 0)
Poster Session 43 - Whats new from the bench: Treating or preventing LUTS
Functional LUTS, incontinence and neuro-urology: Basic science

Introduction & Objectives

Detrusor sphincter dyssynergia (DSD), defined as detrusor contraction concurrent with involuntary contraction of the urethral and/or periurethral striated muscle, is a common and severe sequela of different neurological diseases including spinal cord injury (SCI). It may lead to high intravesical pressure causing structural damage to the lower and upper urinary tract with a relevant risk for life-threatening end-stage renal failure but no causal therapy is currently available for this dangerous condition. Thus, our objective was to investigate if antibodies against the nerve fiber growth inhibitory central nervous system protein Nogo-A applied to the injured spinal cord in rats could prevent the development of lower urinary tract dysfunction, in particular DSD.

Materials & Methods

Lower urinary tract function of 86 female Lewis rats with no injury (n=17) complete (n=28) or incomplete (n=41) spinal cord injury at thoracic level 8 was assessed using our novel urodynamic model (Schneider MP et al., BJUI 2015) allowing repetitive longitudinal measurements of both bladder and external urethral sphincter function in the same animal under fully awake conditions.


Four weeks after large but incomplete thoracic SCI, DSD had developed in all untreated (n=15) or control antibody infused (n=17) animals. In contrast, 2 weeks of intrathecal anti-Nogo-A-antibody treatment (n=16) lead to a highly significant reduction of maximum detrusor pressure during voiding (mean difference to control 32 cmH2O, 50% change, p<0.001) and of EMG high-frequency activity in the external urethral sphincter (mean difference to control 21%, 41% change, p=0.002).


Our findings indicate that anti-Nogo-A-antibody treatment has beneficial effects on the lower urinary tract in rats re-establishing a physiological status and preventing DSD after incomplete SCI, presumably by influencing the neuronal wiring of descending micturition circuits. Thus, anti-Nogo-A immunotherapy, which currently enters new clinical trials in humans, could become a unique causal treatment option for lower urinary tract dysfunction in patients with SCI.