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
Bibliographic record
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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.002 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".