DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for lower urinary tract calculus — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleLower urinary tract calculus maps to a 35-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 lower urinary tract calculus 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
regulator of G protein signaling 17 (RGS17) — RGS17 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 pgedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6AM3 · 1.53 Å · ligand TRIETHYLENE GLYCOL (PGE). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts cover several distinct lower urinary tract conditions, not a single disease. One large prospective cohort study of 25,879 US men without prior surgery or medication reported that the age-standardised incidence of moderate-to-worse lower urinary tract symptoms (International Prostate Symptom Score 15 or greater, surgery, or medication) was 18.5 per 1,000 man-years, and the incidence of modest-or-worse symptoms (score 8 or greater) was 40.5 per 1,000 man-years. Among 9,628 men who already had modest symptoms, the progression rate to severe symptoms (score 20 or greater, surgery, or medication) was 44.9 per 1,000 man-years. Both incidence and progression increased steeply with age (p trend <0.0001). The authors note these rates could be used to plan trials of lifestyle interventions.
A separate pilot study in female CBA/J mice tested a synthetic derivative of antiproliferative factor (as-APF), a glycopeptide made by bladder epithelial cells from patients with interstitial cystitis/painful bladder syndrome. After the bladder epithelium was stripped with acetic acid, daily intravesical as-APF significantly attenuated epithelial repair compared to control peptide or phosphate-buffered saline on days 3 through 21 (p < 0.05). Mean epithelial area over all measured days was significantly lower in as-APF-treated mice than in either control group (p < 0.0001). Expression of uroplakin III and zonula occludens type 1 was also decreased in as-APF-treated mice by day 7 and day 14, respectively. The authors propose this model may be useful for studying the pathophysiology of interstitial cystitis and testing potential therapies, but no human treatment data are provided.
A review of neurostimulation devices for overactive bladder states that sacral nerve stimulation and percutaneous posterior tibial nerve stimulation have shown proven efficacy in high-quality studies. Sacral anterior root stimulation has evidence-based efficacy in spinal cord patients and improves quality of life. Transcutaneous electrical nerve stimulation appears inferior to those treatments but is noninvasive. Results from experimental therapies such as pudendal nerve stimulation are described as promising but needing larger study cohorts. The review does not report specific response or survival rates.
One randomised trial of 306 patients with urinary calculus compared a modified Dihuang decoction (149 patients) given for six years against no intervention (157 patients). Relapse occurred in 8 patients (5.4%) in the treatment group and 46 patients (29.3%) in the control group (P < 0.01). The abstract does not describe the composition of the decoction, the method of stone removal or destruction, or any adverse events. No other abstracts address drug repurposing for lower urinary tract calculus. What remains missing are adequately powered, blinded, placebo-controlled trials with standardised herbal preparations, validated patient stratification (e.g., by stone composition or metabolic risk factors), and long-term follow-up that includes adverse event monitoring.
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 · 2012 · 120 citations
Incidence and Progression of Lower Urinary Tract Symptoms in a Large Prospective Cohort of United States Men
AbstractPURPOSE: To support trials testing lifestyle interventions for lower urinary tract symptoms, often a consequence of benign prostatic hyperplasia, we estimated the incidence and progression rates of lower urinary tract symptoms in United States men unselected for benign prostatic hyperplasia. MATERIALS AND METHODS: We studied men in the HPFS (Health Professionals Follow-Up Study) whom we asked to report periodically by mailed survey whether they had undergone surgery or used medications for lower urinary tract symptoms and to complete the International Prostate Symptom Score survey. For incidence we included 25,879 men with an International Prostate Symptom Score of 0 to 7 and no surgery history who were followed from 1992 to 2008. Incident moderate or worse lower urinary tract symptoms (6,058) were defined as an International Prostate Symptom Score of 15 or greater, surgery, or medication use. Modest or worse lower urinary tract symptoms were similarly defined but with an International Prostate Symptom Score of 8 or greater (11,352). For progression we included 9,628 men with an International Prostate Symptom Score of 8 to 14 and no surgery who were followed from when they first reported an International Prostate Symptom Score of 8 to 14 until 2008. Progression to severe lower urinary tract symptoms (2,557) was defined as an International Prostate Symptom Score of 20 or greater, surgery, or medication use. We estimated age specific and age standardized rates. RESULTS: Incidence and progression rates increased with age (p trend <0.0001), and progression rates were higher than incidence rates. The age standardized rates were incidence of moderate to worse lower urinary tract symptoms 18.5, incidence of modest or worse lower urinary tract symptoms 40.5 and progression to severe lower urinary tract symptoms 44.9 per 1,000 man-years. CONCLUSIONS: The incidence and progression rates of lower urinary tract symptoms are high and increase steeply as men age. These rates may be used for planning adequately powered trials to test lifestyle interventions for lower urinary tract symptoms well before surgical or pharmacological treatment is indicated.
A mouse model for interstitial cystitis/painful bladder syndrome based on APF inhibition of bladder epithelial repair: a pilot study
AbstractBACKGROUND: Interstitial cystitis/painful bladder syndrome (IC/PBS) is a chronic bladder disorder with bladder epithelial thinning or ulceration, pain, urinary frequency and urgency. There is no reliably effective therapy for IC/PBS, and no generally accepted animal model for the disorder in which potential therapies can be tested. Bladder epithelial cells from IC/PBS patients make a small glycopeptide antiproliferative factor or "APF" that inhibits proliferation, decreases tight junction protein expression, increases paracellular permeability, and induces changes in gene expression of bladder epithelial cells in vitro that mimic abnormalities in IC/PBS patient biopsy specimens in vivo. We therefore determined the ability of a synthetic APF derivative to inhibit bladder epithelial repair in mice. METHODS: The bladder epithelium of female CBA/J mice was stripped by transurethral infusion of 3% acetic acid, and mice were subsequently treated daily with one of three intravesical treatments [synthetic as-APF, inactive unglycosylated control peptide, or phosphate buffered saline carrier (PBS)] for 1-21 days. Fixed bladder sections were either stained with haematoxylin and eosin for determination of epithelial area by image analysis, or incubated with anti-uroplakin III (UPIII) or anti-zonula occludens type 1 (ZO-1) antibodies for immunofluorescence microscopy. Epithelial measurement data were analyzed by a two-way analysis of variance (ANOVA); post hoc comparisons of multiple groups were carried out using the Tukey-Kramer method. RESULTS: Bladder epithelial repair was significantly attenuated in as-APF-treated mice as compared to control mice on days 3-21 (p < 0.05); the mean epithelial/total area over all measured days was also significantly lower in as-APF-treated mice vs. mice in either control group by post hoc analysis (p < 0.0001 for both comparisons). UPIII and ZO-1 expression was also decreased in as-APF-treated mice as compared to mice in either control group by day 7 (UPIII) or day 14 (ZO-1). CONCLUSIONS: This model demonstrates in vivo effects of as-APF which abrogates bladder epithelial repair and expression of UPIII and ZO-1 in CBA/J mice following transurethral acetic acid infusion. As bladder epithelial thinning, decreased UPIII expression, and decreased ZO-1 expression are histopathologic features of IC/PBS patient biopsies, this model may be useful for studying the pathophysiology of IC/PBS and the effect of potential therapies.
Medical Devices Evidence and Research · 2017 · 33 citations · open access
Clinical utility of neurostimulation devices in the treatment of overactive bladder: current perspectives
AbstractOBJECTIVES: This review describes the evidence from established and experimental therapies that use electrical nerve stimulation to treat lower urinary tract dysfunction. METHODS: Clinical studies on established treatments such as percutaneous posterior tibial nerve stimulation (P-PTNS), transcutaneous electrical nerve stimulation (TENS), sacral nerve stimulation (SNS) and sacral anterior root stimulation (SARS) are evaluated. In addition, clinical evidence from experimental therapies such as dorsal genital nerve (DGN) stimulation, pudendal nerve stimulation, magnetic nerve stimulation and ankle implants for tibial nerve stimulation are evaluated. RESULTS: SNS and P-PTNS have been investigated with high-quality studies that have shown proven efficacy for the treatment for overactive bladder (OAB). SARS has proven evidence-based efficacy in spinal cord patients and increases the quality of life. TENS seems inferior to other OAB treatments such as SNS and P-PTNS but is noninvasive and applicable for ambulant therapy. Results from studies on experimental therapies such as pudendal nerve stimulation seem promising but need larger study cohorts to prove efficacy. CONCLUSION: Neurostimulation therapies have proven efficacy for bladder dysfunction in patients who are refractory to other therapies. SIGNIFICANCE: Refinement of neurostimulation therapies is possible. The aim should be to make the treatments less invasive, more durable and more effective for the treatment of lower urinary tract dysfunction.
Current Opinion in Obstetrics & Gynecology · 1992 · 1 citations
Investigative techniques, assessment of incontinence, and urodynamics
AbstractThe past year's literature reflects a continued interest in studying and refining standard investigative techniques, both urodynamic and radiographic, that have long been used to evaluate patients with lower urinary tract dysfunction. In addition, new, simple, and inexpensive technologies that allow relatively accurate diagnosis and that minimize medical costs have been introduced. These continued efforts to understand the pathophysiology of the lower urinary tract better bring both the practicing physician and the urogynecologist closer to making correct diagnoses and appropriate therapeutic decisions.
Study on the Prevention of Relapse of Urinary Calculus with Modified Dihuang Decoction
AbstractObjective To studythe preventive effects of modified Dihuang decoction on the relapse of urinary calculus after caiculus removed or destroyed.Methods 306 cases were randomly divided into a trealment group (with 149 cases)and a control group(with 157 cases).The trealment group was interfered with modified Dihuang decoction for 6 years,and the control group was not interfered with any medicine.Observe the relapse number in the two groups.Results There were 8 cases relapsed in the treatment group(5.4%)comparing with 46 cases relapsed in the control group(29.3%),showing a significant difference (P＜0.01).Conclusion Medified Dihuang decoction has apparent effects in preventing relapse of urinary calculus.
Key words:
Urinary Calculus; Modified Dihuang decoction; Prevention
Contractile activity of the bladder urothelium and lamina propria
AbstractThis project involves investigating the receptors, genes and neuronal systems modulating a unique contractile activity generated from within the bladder wall. The activity may be an underlying cause of lower urinary tract diseases and this research has identified a range of novel therapeutic targets which can be clinically utilised for therapeutic treatments.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
