DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for chronic interstitial cystitis — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleChronic interstitial cystitis maps to a 3-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for chronic interstitial cystitis is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
adrenoceptor beta 3 (ADRB3) — ADRB3 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet aledrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9IJE · 2.34 Å · ligand L-EPINEPHRINE (ALE). Experimental structure, not a prediction.
What the evidence adds up to
The Interstitial Cystitis Data Base study followed 637 eligible patients, of whom more than 90% were white women with a median age of 43 years. Median follow-up was 31 months. Using an overall pain-urgency-frequency score, 7% presented with mild, 44% with moderate, and 49% with severe symptoms. Severe urgency in 41% and severe 24-hour frequency in 41% were more common than severe pain in 29%. Median duration of symptoms was 8 years. The 36% of patients who withdrew or were lost to follow-up had more severe symptoms at baseline. Although all symptoms fluctuated, there was no evidence of significant long-term change in overall disease severity. The authors concluded that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time.
In a separate study of 65 female patients and 40 age-matched healthy controls, patients reported compromised quality of life across physical functioning, role function, and vitality, and had more severe depressive symptoms on the Beck Depression Inventory and the Hamilton Rating Scale for Depression. Greater interstitial cystitis severity was associated with greater compromise in physical and social functioning and mental health, but not in other quality of life domains or depressive symptoms. The pathogenesis of interstitial cystitis remains uncertain, and the illness has significant diversity. Dysfunction of the immune system, inflammatory processes, and bladder structure and neuromuscular function have all been implicated, but current therapy can only treat symptoms, not the cause.
A 2021 gene expression analysis of ulcerative interstitial cystitis identified 216 up-regulated and 267 down-regulated differentially expressed genes, and proposed CXCL8, CXCL1, and IL6 as potential biomarkers. However, this is a bioinformatics study without clinical validation. The American Urological Association guidelines separate treatment into six tiers of increasing invasive therapies, beginning with education and lifestyle modifications and progressing through physical, pharmacological, and ultimately surgical therapies. A universally effective pharmacological regimen has not been reported.
What remains missing is a definitive understanding of disease aetiopathogenesis, validated biomarkers to stratify patients into subtypes that share common processes, and a trial design that can demonstrate a significant long-term impact on disease severity rather than short-term symptom fluctuation. Funding for adequately powered, placebo-controlled trials with standardised endpoints and long follow-up is still lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
The Journal of Urology · 2000 · 179 citations
A PROSPECTIVE STUDY OF INTERSTITIAL CYSTITIS: RESULTS OF LONGITUDINAL FOLLOWUP OF THE INTERSTITIAL CYSTITIS DATA BASE COHORT
AbstractPURPOSE: We present baseline characteristics and longitudinal profiles of symptoms in the Interstitial Cystitis Data Base study, a prospective cohort study of patients with interstitial cystitis. MATERIALS AND METHODS: A total of 637 eligible patients were entered into the study and followed for symptoms of pain, urgency and urinary frequency. Median followup was 31 months. RESULTS: More than 90% of patients were white women with a median age of 43 years. Using the overall pain-urgency-frequency score 7% of participants presented with mild, 44% with moderate and 49% with severe symptoms. Severe urgency in 41% of cases and severe 24-hour frequency in 41% were more common than severe pain in 29%. Of the patients 51% reported nighttime frequency of 2 or more voids. Median duration of interstitial cystitis symptoms was 8 years and 68% of participants were previously diagnosed with the condition. The 36% of patients who withdrew from study or were lost to followup were more likely to have had more severe symptoms at baseline. Patterns of change with time suggest initial symptom improvement due to regression to the mean, and an intervention effect associated with the increased followup and care of cohort participants. Although all symptoms fluctuated, there was no evidence of significant long-term change in overall disease severity. CONCLUSIONS: Our observations support the clinical observation that interstitial cystitis is a chronic disease and no current treatments have a significant impact on symptoms with time. These results provide a foundation for the design and performance of future clinical trials in interstitial cystitis using these end points in a similar patient population.
Depressive Symptoms And Quality Of Life In Patients With Interstitial Cystitis
AbstractPURPOSE: Previous research suggests that patients with interstitial cystitis have poorer quality of life and higher levels of depressive symptoms. However, most studies to date have been limited by the lack of standard measures to describe the experience of living with interstitial cystitis. In addition, to our knowledge no study has used a structured interview to assess depressive symptomatology. We investigated the extent of depressive symptoms and impaired quality of life in a sample of female patients with interstitial cystitis compared with healthy controls. Relationships among physician rated symptom severity, quality of life and depressive symptoms were also examined. MATERIALS AND METHODS: At a clinic visit 65 female patients previously diagnosed with interstitial cystitis and 40 age matched, healthy controls completed questionnaires on depressive symptoms (Beck Depression Inventory) and quality of life (Medical Outcomes Study 36-Item Short Form), and a structured interview on depressive symptoms (Hamilton Rating Scale for Depression) with trained interviewers. RESULTS: Patients reported compromised quality of life compared with healthy controls across various domains, including physical functioning, ability to function in one's normal role and vitality. They also had more severe depressive symptoms on the 2 depression measures. In patients, greater interstitial cystitis severity was associated with greater compromise in physical and social functioning, and mental health but not in other quality of life domains or depressive symptoms. CONCLUSIONS: A diagnosis of interstitial cystitis is related to poorer functioning in various life domains. Decrements increase with disease severity.
Current Opinion in Infectious Diseases · 2006 · 27 citations
Interstitial cystitis pathogenesis and treatment
AbstractPURPOSE OF REVIEW: Interstitial cystitis remains an idiopathic illness characterized by urinary frequency, urgency and pelvic pain with substantial morbidity in those affected. There is significant variability in the presentation, severity of symptoms and response to therapy. This review focuses on recent findings on the possible pathogenesis and potential treatments for this disease. RECENT FINDINGS: Interstitial cystitis is manifested by sensory hypersensitivity. A small volume of urine will be associated with an exaggerated sensation of pain or pressure and urinary urgency. There is continued research regarding how this process is initiated and maintained and to what extent systemic dysfunction of the immune or autonomic nervous system may play a role. The urothelial lining has been demonstrated to be capable of secreting a large number of potential signaling molecules that may be significant factors in the disease. SUMMARY: The pathogenesis of interstitial cystitis remains uncertain and the illness has significant diversity. Additional research is needed to establish subtypes that share common processes that can be targeted for treatment as a single effective therapy for the condition remains elusive.
AbstractInterstitial cystitis (IC) is a serious debilitating disease often overlooked by medical and health professionals. This paper describes the elusive aetiology and the painful symptoms of IC and how it affects the patient's life. The author outlines the treatments available and offers guidelines for supporting patients with the disease.
Current guidelines in the management of interstitial cystitis.
AbstractInterstitial cystitis (IC) is a heterogeneous chronic disease of unknown etiology that impacts a very large number of women. Symptoms are highly variable: patients may suffer from pelvic pain that is exacerbated by bladder filling, and can be associated with a variety of lower urinary tract symptoms including frequency and urgency. Given the varying presentations and severities of corresponding treatment must be tailored to each specific patient. Current American Urological Association (AUA) guidelines separate the IC treatment recommendations into six tiers of increasing invasive therapies. These treatment guidelines begin with education and lifestyle modifications and progress through levels of physical, pharmacological, and ultimately surgical therapies for those that fail the less invasive therapies. The purpose of this review is to outline the recommendations for the treatment of IC and the evidence from which these recommendations arise. Furthermore, we examine the most up to date literature so that we may recognize future directions in the treatment of IC.
AbstractLittle is known about the etiology of interstitial cystitis. Dysfunction of the immune system, inflammatory processes, and structure and neuromuscular function of the bladder have all been implicated. The evidence for each is reviewed. Current therapy is limited because it can only treat the symptoms of this disease, and not the cause.
International braz j urol · 2021 · 6 citations · open access
Exploration of the core genes in ulcerative interstitial cystitis/bladder pain syndrome
AbstractOBJECTIVE: Interstitial cystitis (IC)/bladder pain syndrome (BPS) is a chronic inflammatory disease that can cause bladder pain and accompanying symptoms, such as long-term urinary frequency and urgency. IC/BPS can be ulcerative or non-ulcerative. The aim of this study was to explore the core genes involved in the pathogenesis of ulcerative IC, and thus the potential biomarkers for clinical treatment. MATERIALS AND METHODS: First, the gene expression dataset GSE11783 was downloaded using the Gene Expression Omnibus (GEO) database and analyzed using the limma package in R to identify differentially expressed genes (DEGs). Then, the Database for Annotation, Visualization and Integrated Discovery (DAVID) was used for Gene Ontology (GO) functional analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) was used for pathway enrichment analysis. Finally, the protein-protein interaction (PPI) network was constructed, and key modules and hub genes were determined using the STRING and Cytoscape software. The resulting key modules were then analyzed for tissue-specific gene expression using BioGPS. RESULTS: A total of 216 up-regulated DEGs and 267 down-regulated genes were identified, and three key modules and nine hub genes were obtained. CONCLUSION: The core genes (CXCL8, CXCL1, IL6) obtained in this study may be potential biomarkers of interstitial cystitis with guiding significance for clinical treatment.
Expert Opinion on Pharmacotherapy · 2003 · 3 citations
Current status in the pharmacological management of interstitial cystitis
AbstractInterstitial cystitis is a clinical condition occurring predominantly in women characterised by irritative voiding symptoms in the form of urinary frequency, urgency and pain. Patient symptoms have the potential to significantly affect quality of life, posing a challenge to some to perform activities of daily living. Those who reach an eventual diagnosis of interstitial cystitis have typically done so through an emotionally charged and circuitous route, the product of numerous physician encounters and stigmatising experiences. As such, these patients require considerate care. Overall, current pharmacological agents for the treatment of those with interstitial cystitis, provide a measure of symptomatic benefit, however, a universally effective regimen remains to be reported. As a definitive disease aetiopathogenesis is not fully determined, trials of pharmacological therapy are ongoing.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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