DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for bladder exstrophy — screening already-approved drugs against its 26-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBladder exstrophy maps to a 26-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 bladder exstrophy 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
RAB23, member RAS oncogene family (RAB23) — RAB23 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8YL3 · 1.2 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
From 1989 to 1997, 18 patients with bladder exstrophy and 6 with cloacal exstrophy underwent complete primary repair of exstrophy, with a mean follow-up of 44 months. At a median follow-up of 48 months, 4 boys and 4 girls had volitional voiding after repair, 21 patients had continent intervals, and no patient lost renal function. Urethrocutaneous fistula occurred in 2 cases; no primary closure dehiscence was observed. A later report on the same technique with longer follow-up (median 106 months in the original group, 58 months in the entire series of 39 children) found that 74% of children aged 4 years or older achieved daytime continence with volitional voiding. Primary urinary continence without bladder neck reconstruction was achieved in 20% of boys and 43% of girls; an additional 18% of boys and girls achieved continence with only bladder neck injection. Complications developed in 7 of 39 children (18%).
A nationwide database study from 1988 to 2000 identified 407 cases of surgical repair of bladder exstrophy. Mean length of hospital stay was 24.6 days, and mean inflation-adjusted hospital charges were $62,302. High-volume hospitals (5 or more cases per year) had lower charges ($37,370) than mid-volume ($51,778) or low-volume hospitals ($50,474). Six patients died after repair (1.5%), all born prematurely. Premature births were more common at low-volume hospitals (11.1%) than at high-volume (4.2%) or mid-volume hospitals (5.9%). The authors note that variations in practice patterns and case mix may contribute to differences in resource use and outcomes.
A study of bladder biopsies from 32 infants with bladder exstrophy-epispadias complex taken at primary closure found gross histological alterations with inflammatory, proliferative and metaplastic changes in most specimens. Uroplakin IIIa and cytokeratin 20 were absent in 76% of tissues examined, while cytokeratin 13 was expressed in all specimens. Irregular expression of tight junction protein claudin 4 was seen in 52% of biopsies. The authors suggest that abnormal urothelial differentiation may result in a dysfunctional urothelial barrier, potentially affecting the structural and functional properties of the bladder template after closure, but note that the underlying cause remains unknown.
What is still missing is a clear understanding of why urothelial differentiation is abnormal in most exstrophic bladders and whether this can be influenced. No randomised trial compares complete primary repair with staged repair for continence or complications. The database study shows that outcomes vary with hospital volume and patient mix, but the data are observational and from the 1990s. No drug therapy is tested in these abstracts; anticholinergic medication is mentioned only in passing as an adjunct, without evidence from these studies.
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 · 1999 · 225 citations
COMPLETE PRIMARY REPAIR OF EXSTROPHY
AbstractPURPOSE: The surgical correction of bladder exstrophy to achieve continence with voiding remains a challenging problem for the urologist. Since 1989 we have performed complete primary repair for exstrophy based on the concept that the primary defect of bladder and cloacal exstrophy is anterior herniation. Thus, the bladder and urethra must be treated as a single unit to move them posteriorly into the pelvis. We present this technique. MATERIALS AND METHODS: From 1989 to 1997, 18 patients with bladder exstrophy and 6 with cloacal exstrophy underwent complete primary repair of exstrophy. This procedure was done on day 1 of life in 18 patients. Mean followup is 44 months (range 4 months to 8 years). RESULTS: At a median followup of 48 months 4 boys and 4 girls have volitional voiding after complete primary repair of bladder exstrophy, 21 patients have continent intervals and 2 boys void with continent intervals after complete primary repair of cloacal exstrophy. No patient has had a loss of renal function in this series. Postoperative complications included urethrocutaneous fistula formation in 2 cases. No patient had primary closure dehiscence. CONCLUSIONS: The rate of urinary continence achieved with complete primary repair compares favorably to that of staged repair for exstrophy. Complete primary repair also minimizes the number of surgical procedures required to achieve urinary continence and potentiates bladder neck function that permits bladder cycling in year 1 of life. The complication rates of these techniques are significantly lower than those reported in previous series of primary closure of exstrophy.
SURGICAL REPAIR OF BLADDER EXSTROPHY IN THE MODERN ERA: CONTEMPORARY PRACTICE PATTERNS AND THE ROLE OF HOSPITAL CASE VOLUME
AbstractPURPOSE: Bladder exstrophy is a rare condition, and data are lacking regarding practice patterns in its surgical management. We used a large nationwide database to investigate practice patterns of bladder exstrophy repair. MATERIALS AND METHODS: We used the Nationwide Inpatient Sample (1988 to 2000) to identify patients who underwent surgical repair of bladder exstrophy (International Classification of Disease-9 code 578.6). We analyzed factors affecting practice patterns and outcomes. Hospital volume was based on caseload during the highest volume year of study participation (high volume 5 or more, mid volume 3 to 4 and low volume less than 3 cases). RESULTS: We identified 407 cases. Approximately half of the patients (53.2%) were hospitalized within 24 hours of birth, although 28% of patients were older than 1 year. Of the patients 54% were male. Exstrophy repair is extremely resource intensive. In this series mean length of hospital stay (LOS) was 24.6 +/- 22.8 days, and mean inflation adjusted hospital charges were 62,302 dollars (median 39,978 dollars). High volume hospitals (HVHs) had lower hospital charges (37,370 dollars) than mid volume (51,778 dollars) or low volume hospitals (LVHs, 50,474 dollars, p = 0.0095). On multivariate regression HVHs had lower charges even after controlling for other significant predictors, including LOS (p <0.0001). Patients at HVHs were more likely to undergo osteotomy (p = 0.007). Six patients died after exstrophy repair (1.5%), all of whom had been born prematurely (p <0.0001). Although death was more likely at LVHs, this was due to the fact that more patients at LVHs were born prematurely (4.2% at HVHs vs 5.9% at mid volume hospitals and 11.1% at LVHs, p = 0.027). CONCLUSIONS: Bladder exstrophy repair carries a high risk of morbidity and is resource intensive. Variations between high and low volume hospitals in practice patterns and case mix may contribute to observed differences in resource use, LOS and clinical outcomes.
Long-Term Followup of Complete Primary Repair of Exstrophy: The Seattle Experience
AbstractPURPOSE: Since 1989, we have used the complete primary repair of exstrophy surgical technique to reconstruct the genitourinary system of children born with the exstrophy-epispadias complex based on the assumption that this complex represents a malformation. We initially reported using this technique in 1999. We now report a longer term followup of this initial group as well as surgical outcomes in a larger group of children who have undergone this repair for classic bladder exstrophy. MATERIALS AND METHODS: Since 1989, we have prospectively followed 39 children who underwent the complete primary repair of exstrophy technique to construct classic bladder exstrophy. Median followup in the original group of patients that we reported in 1999 is 106 months. Median followup in the entire series is 58 months. RESULTS: Of boys and girls 4 years or older 74% have achieved daytime continence with volitional voiding. Of boys and girls 20% and 43%, respectively, have achieved primary urinary continence without the need for bladder neck reconstruction. An additional 18% of boys and girls achieved continence with only bladder neck injection following complete primary repair of exstrophy. Complications developed in 7 of the 39 children (18%) in the entire series. CONCLUSIONS: Urinary continence has been consistently achieved with this form of exstrophy repair. Primary continence without the need for further reconstruction is possible. The results of this patient series have caused us to modify the complete primary repair of exstrophy technique in an effort to improve the rate of primary urinary continence.
AbstractPURPOSE OF REVIEW: The patient with bladder exstrophy presents complex surgical and clinical management challenges to the pediatric urologist. This review aims to present recent developments in the care of these patients as well as to review contemporary medical outcomes. RECENT FINDINGS: Most of the early literature pertaining to bladder exstrophy has focused on surgical techniques and management. In the last 10-20 years, however, there has been an increase in the number of publications dealing with long-term outcomes in these patients. Psychosexual development, sexual function and social adaptation have received as much attention as urinary continence status, bladder, and renal function. This review will examine these topics. SUMMARY: Despite the complex nature of bladder exstrophy, there are no well designed, prospective trials examining clinical outcomes in these patients. Until better trials are planned, executed and published, much of what we know about patients with bladder exstrophy will be based on retrospective observations with significant biases.
Expression and Potential Clinical Significance of Urothelial Cytodifferentiation Markers in the Exstrophic Bladder
AbstractPURPOSE: We characterize the urothelium from patients with classic bladder exstrophy-epispadias complex for the expression of proteins associated with urothelial differentiation, and discuss a potential impact of urothelial phenotype on the structural and functional properties of the bladder template following bladder closure. MATERIALS AND METHODS: From 2005 to 2010 bladder biopsies from 32 infants with bladder exstrophy-epispadias complex obtained at primary bladder closure were collected. After histological assessment immunochemistry was used to investigate the expression of uroplakin IIIa, cytokeratin differentiation restricted antigens CK13 and CK20, and tight junction protein claudin 4. RESULTS: Overall tissue morphology showed gross alterations with inflammatory, proliferative and metaplastic changes in most specimens. Sections of intact epithelium were present in 78% of biopsies. With respect to urothelial phenotype, CK13 was expressed in all specimens, whereas UPIIIa and CK20 were absent in 76% of the tissues examined. Of the biopsies 52% revealed an irregular expression pattern of tight junction protein Cl-4. CONCLUSIONS: This is the first study to our knowledge to characterize the urothelium from infants with bladder exstrophy-epispadias complex for the expression of urothelial differentiation associated antigens. Our findings suggest urothelial differentiation changes in a majority of exstrophic bladders, at least at primary bladder closure. Although the underlying etiology remains to be established, abnormal urothelial differentiation may result in a dysfunctional urothelial barrier with implications for the structural and functional properties of the bladder template. Despite the study limitations, our preliminary findings provide a platform for further investigation of the significance of the urothelium for the exstrophic bladder.
AbstractSurgical management of bladder exstrophy demands patience and perseverance. It is possible to provide all patients with socially acceptable continence with bladder neck division and catheterizable continent stoma as the last resort. Urodynamic assessment has emerged as an essential tool in the follow-up evaluation of these patients. Anticholinergic medication with imipramine or oxybutinin is a useful adjunct in the overall management.
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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