Anti-Nogo-A Antibodies As a Potential Causal Therapy for Lower Urinary Tract Dysfunction after Spinal Cord Injury
| Autor: | Martin E. Schwab, Thomas M. Kessler, Andrea M. Sartori, Anne K. Engmann, Benjamin V. Ineichen, Marc P. Schneider, Anna-Sophie Hofer, Oliver Weinmann, Selina Moors |
|---|---|
| Přispěvatelé: | University of Zurich, Schneider, Marc P |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Nogo Proteins Urinary system media_common.quotation_subject Urology 610 Medicine & health Inhibitory postsynaptic potential Urination Antibodies 03 medical and health sciences 0302 clinical medicine Animals Medicine Urinary Bladder Neurogenic Spinal cord injury Research Articles Spinal Cord Injuries media_common business.industry General Neuroscience Urethral sphincter 2800 General Neuroscience medicine.disease Rats Clinical trial 030104 developmental biology Rats Inbred Lew 10046 Balgrist University Hospital Swiss Spinal Cord Injury Center Female business Detrusor sphincter dyssynergia 030217 neurology & neurosurgery Lumbosacral joint |
| Zdroj: | The Journal of Neuroscience. 39:4066-4076 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.3155-18.2019 |
| Popis: | Loss of bladder control is common after spinal cord injury (SCI) and no causal therapies are available. Here we investigated whether function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe SCI could prevent development of neurogenic lower urinary tract dysfunction. Bladder function of rats with SCI was repeatedly assessed by urodynamic examination in fully awake animals. Four weeks after SCI, detrusor sphincter dyssynergia had developed in all untreated or control antibody-infused animals. In contrast, 2 weeks of intrathecal anti-Nogo-A antibody treatment led to significantly reduced aberrant maximum detrusor pressure during voiding and a reduction of the abnormal EMG high-frequency activity in the external urethral sphincter. Anatomically, we found higher densities of fibers originating from the pontine micturition center in the lumbosacral gray matter in the anti-Nogo-A antibody-treated animals, as well as a reduced number of inhibitory interneurons in lamina X. These results suggest that anti-Nogo-A therapy could also have positive effects on bladder function clinically.SIGNIFICANCE STATEMENTAfter spinal cord injury, loss of bladder control is common. Detrusor sphincter dyssynergia is a potentially life-threatening consequence. Currently, only symptomatic treatment options are available. First causal treatment options are urgently needed in humans. In this work, we show that function-blocking antibodies against the nerve-fiber growth inhibitory protein Nogo-A applied to rats with severe spinal cord injury could prevent development of neurogenic lower urinary tract dysfunction, in particular detrusor sphincter dyssynergia. Anti-Nogo-A therapy has entered phase II clinical trial in humans and might therefore soon be the first causal treatment option for neurogenic lower urinary tract dysfunction. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|