Toby C. Chai

Aims: In April of 2025, the Wake Forest Institute for Regenerative Medicine hosted a Global Consensus meeting on IC/BPS in Winston‐Salem, NC. The goal of this meeting was to establish global consensus regarding diagnostic criteria, phenotyping, treatment outcome assessment, and etiopathology in interstitial cystitis/bladder pain syndrome (IC/BPS). Our sub‐committee was tasked with developing a consensus document on patient phenotyping in IC/BPS. Methods: Narrative review. Results: Patients with IC/BPS populate broad groups that have been characterized as having a bladder‐focused disease phenotype (bladder‐centric), a widespread pain and symptoms phenotype (systemic), or by other variable phenotypes including those with myofascial pelvic pain. In this review, we discuss the published evidence supporting each of these patient phenotypic groups. Conclusions: Future clinical trials and treatment development in IC/BPS should include patient phenotyping efforts with, at minimum, a focus on stratification into bladder‐centric vs systemic and efforts to refine discriminative thresholds (cut‐off points) that may influence differential treatment outcomes. It is important to continue to investigate the importance of patient phenotypes on treatment strategy selection, outcomes, and our understanding of the underlying pathophysiology for this disease spectrum. Clinical Trial Registration: N/A.

Objectives: Much of the information to date in terms of subtypes and function of bladder urothelial cells were derived from anatomical location or by the expression of a small number of marker genes. To have a comprehensive map of the cellular anatomy of bladder urothelial cells, we performed single‐cell RNA sequencing to thoroughly characterize mouse bladder urothelium.Materials and methods: A total of 18,917 single cells from mouse bladder urothelium were analysed by unbiased single‐cell RNA sequencing. The expression of the novel cell marker was confirmed by immunofluorescence using urinary tract infection models.Results: Unsupervised clustering analysis identified 8 transcriptionally distinct cell subpopulations from mouse bladder urothelial cells. We discovered a novel type of bladder urothelial cells marked by Plxna4 that may be involved with host response and wound healing. We also found a group of basal‐like cells labelled by ASPM that could be the progenitor cells of adult bladder urothelium. ASPM⁺ urothelial cells are significantly increased after injury by UPEC. In addition, specific transcription factors were found to be associated with urothelial cell differentiation. At the last, a number of interstitial cystitis/bladder pain syndrome–regulating genes were found differentially expressed among different urothelial cell subpopulations.Conclusions: Our study provides a comprehensive characterization of bladder urothelial cells, which is fundamental to understanding the biology of bladder urothelium and associated bladder disease.

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Aims: Two phase 1 trials were performed in healthy women with the overactive bladder (OAB) syndrome and urodynamically demonstrated detrusor overactivity (DO), with the aim to demonstrate the safety and potential efficacy of URO‐902, which comprises a gene therapy plasmid vector expressing the human big potassium channel α subunit.Methods: ION‐02 (intravesical instillation) and ION‐03 (direct injection) were double‐blind, placebo‐controlled, multicenter studies without overlap in enrollment between studies. Active doses were administered and evaluated sequentially (lowest dose first) for safety. ION‐02 participants received either 5000 µg or 10 000 µg URO‐902, or placebo. ION‐03 participants received either 16 000 or 24 000 µg URO‐902, or placebo, injected directly into the bladder wall using cystoscopy. Primary outcome variables were safety parameters occurring subsequent to URO‐902 administration; secondary efficacy variables also were evaluated.Results: Among the safety outcomes, there were no dose‐limiting toxicities or significant adverse events (AEs) preventing dose escalation during either trial, and no participants withdrew due to AEs. For efficacy, in ION‐02 (N = 21), involuntary detrusor contractions on urodynamics at 24 weeks in patients receiving URO‐902 (P < .0508 vs placebo) and mean urgency incontinence episodes in the 5000 µg group (P = .0812 vs placebo) each showed a downward trend. In ION‐03 (N = 13), significant reduction versus placebo in urgency episodes (16 000 µg, P = .036; 24 000 µg, P = .046) and number of voids (16 000 µg, −2.16, P = .044; 24 000 µg, −2.73, P = .047) were observed 1 week after injection.Conclusion: Promising safety and efficacy results in these preliminary phase 1 studies suggest gene transfer may be a promising therapy for OAB/DO, warranting further investigation.