Challenges in modeling interstitial cystitis: implications for drug discovery efforts

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition characterized by bladder pain and lower urinary tract symptoms. Despite extensive investigation and numerous therapeutic candidates, few disease-modifying treatments have translated into clinical practice. Evidence indicates that IC/BPS comprises biologically distinct phenotypes, including inflammatory bladder-centric and systemic pain-associated phenotypes, creating challenges for experimental modeling and drug development.

Using literature from a structured search of PubMed, Scopus, and Web of Science, this review examines current IC/BPS model systems from a drug discovery perspective, including preclinical, human translational, and computational approaches. The authors evaluate the biological domains captured by existing models, their strengths and limitations, and their influence on therapeutic development. Attention is given to four translational challenges: inadequate representation of disease heterogeneity, reliance on acute injury paradigms for a chronic pain condition, bladder-centric modeling of a multisystem disorder, and limited integration of computational phenotyping. Finally, the authors propose a model-informed framework linking experimental systems with therapeutic mechanisms, patient phenotypes, and clinically relevant endpoints.

Progress in IC/BPS drug discovery will depend on mechanism-driven use of complementary models aligned with defined patient subgroups. Integrating patient phenotyping, biomarkers, computational methods, and back-translation from clinical trial outcomes may improve translational predictability and therapeutic success.