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

• Published in: Neurourology and urodynamics Vol. 44; no. 3; pp. 577 - 584
• Main Authors: Sinha, Sanjay, Cruz, Francisco, Cuenca, Esther Martinez, Przydacz, Mikolaj, Kheir, George Bou, Kanai, Anthony J., Van Huele, Andries, Gajewski, Jerzy B., Tarcan, Tufan, Lazar, Jason M., Weiss, Jeffrey P., Tyagi, Pradeep, Abrams, Paul, Wein, Alan
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.03.2025
• Subjects: acontractile detrusor; Animals; Bladder; Bombesin; Cell therapy; Clinical trials; Humans; lower urinary tract symptoms; Molecular Targeted Therapy; Myocytes; Neurokinin; Regeneration; Senescence; Stem Cell Transplantation - methods; Stem cells; underactive; underactive detrusor; Urethra; Urinary bladder; Urinary Bladder - innervation; Urinary Bladder - physiopathology; Urinary Bladder, Underactive - physiopathology; Urinary Bladder, Underactive - therapy; urodynamics; Urothelium; acontractile detrusor; underactive detrusor; underactive; urodynamics; lower urinary tract symptoms; urinary bladder
• ISSN: 0733-2467; 1520-6777; 1520-6777
• DOI: 10.1002/nau.25597

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.