Is It Possible to Regenerate the Underactive Detrusor? Part 1. Molecular and Stem Cell Therapies Targeting the Urinary Bladder and Neural Axis - ICI-RS 2024.
Sanjay Sinha, Francisco Cruz, Esther Martinez Cuenca, Mikolaj Przydacz, George Bou Kheir, Anthony J Kanai, Andries Van Huele, Jerzy B Gajewski, Tufan Tarcan, Jason M Lazar, Jeffrey P Weiss, Pradeep Tyagi, Paul Abrams, Alan Wein
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引用次数: 0
Abstract
Introduction: Detrusor muscle weakness is commonly noted on urodynamics in patients with refractory voiding difficulty. No approved therapies have been proven to augment the strength of a detrusor voiding contraction.
Methods: This subject was discussed by a think-tank at the International Consultation on Incontinence- Research Society (ICI-RS) meeting held in Bristol, June 2024. The discussions of the think-tank are being published in two parts. This first part discusses molecular and stem cell therapies targeting the urinary bladder and the neural axis.
Results: Senescence of the urothelium and extracellular ATP acting through P2X3 receptors might be important in detrusor underactivity. Several molecules such as parasympathomimetics, acotiamide, ASP8302, neurokinin-2 agonists have been explored but none has shown unequivocal clinical benefit. Different stem cell therapy approaches have been used, chiefly in neurogenic dysfunction, with some studies showing benefit. Molecular targets for the neural axis have included TRPV-4, Bombesin, and serotoninergic receptors and TAC-302 which induces neurite growth.
Conclusions: Several options are currently being pursued in the search for an elusive molecular or stem cell option for enhancing the power of the detrusor muscle. These encompass a wide range of approaches that target each aspect of the contraction mechanism including the urothelium of bladder and urethra, myocyte, and neural pathways. While none of these have shown unequivocal clinical utility, some appear promising. Lessons from other fields of medicine might prove instructive.
Clinical trial registration: Not necessary. Not a clinical trial.
期刊介绍:
Neurourology and Urodynamics welcomes original scientific contributions from all parts of the world on topics related to urinary tract function, urinary and fecal continence and pelvic floor function.