DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for biliary tract disease — screening already-approved drugs against its 38-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBiliary tract disease maps to a 38-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 biliary tract disease 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
nudix hydrolase 3 (NUDT3) — NUDT3 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 ihpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2FVV · 1.25 Å · ligand INOSITOL HEXAKISPHOSPHATE (IHP). Experimental structure, not a prediction.
What the evidence adds up to
In a 2018 phase 3 trial of 100 patients with primary biliary cholangitis who had an inadequate response to ursodeoxycholic acid, 31% of those assigned to bezafibrate 400 mg daily achieved a complete biochemical response at 24 months, compared with 0% assigned to placebo. Normal alkaline phosphatase levels occurred in 67% of the bezafibrate group versus 2% of the placebo group. Two patients in each group had complications from end-stage liver disease. Creatinine increased 5% from baseline with bezafibrate and decreased 3% with placebo; myalgia occurred in 20% of the bezafibrate group and 10% of the placebo group.
A 2023 Chinese regulatory guideline notes that drug options for primary biliary cholangitis remain limited and that clinical trials of multiple drugs with distinct targets are underway. The guideline was issued to standardise trial design, focusing on selection of test populations and efficacy endpoints.
A 2015 systematic review of incidentally found common bile duct dilatation found a cause in 33% of cases on average, most commonly a bile duct stone, chronic pancreatitis, or periampullary diverticulum. The overall bile duct diameter was not associated with finding a causative lesion. Coexisting intrahepatic duct dilation, age, and jaundice were indicators of pathologic lesions. Follow-up in six studies ranged from 6 to 85 months and generally showed no change in diagnosis. The review concludes that long-term outcome is not well defined.
A 2021 review of biliary tract cancer states that most patients present in middle or advanced stages and lose the chance of surgery. Conversion therapy aims to downstage disease to enable radical resection, but the cancer is highly heterogeneous in clinical features, cell origin, histology, and molecular biology, and there is a lack of specific and effective conversion therapy strategies. The review calls for individualised regimens.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2018 · 622 citations · open access
A Placebo-Controlled Trial of Bezafibrate in Primary Biliary Cholangitis
AbstractBACKGROUND: Patients with primary biliary cholangitis who have an inadequate response to therapy with ursodeoxycholic acid are at high risk for disease progression. Fibrates, which are agonists of peroxisome proliferator-activated receptors, in combination with ursodeoxycholic acid, have shown potential benefit in patients with this condition. METHODS: In this 24-month, double-blind, placebo-controlled, phase 3 trial, we randomly assigned 100 patients who had had an inadequate response to ursodeoxycholic acid according to the Paris 2 criteria to receive bezafibrate at a daily dose of 400 mg (50 patients), or placebo (50 patients), in addition to continued treatment with ursodeoxycholic acid. The primary outcome was a complete biochemical response, which was defined as normal levels of total bilirubin, alkaline phosphatase, aminotransferases, and albumin, as well as a normal prothrombin index (a derived measure of prothrombin time), at 24 months. RESULTS: The primary outcome occurred in 31% of the patients assigned to bezafibrate and in 0% assigned to placebo (difference, 31 percentage points; 95% confidence interval, 10 to 50; P<0.001). Normal levels of alkaline phosphatase were observed in 67% of the patients in the bezafibrate group and in 2% in the placebo group. Results regarding changes in pruritus, fatigue, and noninvasive measures of liver fibrosis, including liver stiffness and Enhanced Liver Fibrosis score, were consistent with the results of the primary outcome. Two patients in each group had complications from end-stage liver disease. The creatinine level increased 5% from baseline in the bezafibrate group and decreased 3% in the placebo group. Myalgia occurred in 20% of the patients in the bezafibrate group and in 10% in the placebo group. CONCLUSIONS: Among patients with primary biliary cholangitis who had had an inadequate response to ursodeoxycholic acid alone, treatment with bezafibrate in addition to ursodeoxycholic acid resulted in a rate of complete biochemical response that was significantly higher than the rate with placebo and ursodeoxycholic acid therapy. (Funded by Programme Hospitalier de Recherche Clinique and Arrow Génériques; BEZURSO ClinicalTrials.gov number, NCT01654731 .).
Journal of Clinical Gastroenterology · 2015 · 47 citations
Incidentally Identified Common Bile Duct Dilatation
AbstractBACKGROUND: With the widespread use of abdominal imaging, an incidentally found dilated common bile duct (CBD) is a common radiographic finding. The significance of a dilated CBD as a predictor of underlying disease and long-term outcome have not been well elucidated. GOALS: A systematic review of studies on patients with dilated CBD was performed to identify etiologies and clinical factors that may predict which patients require further diagnostic testing and long-term outcomes. A PubMed search for relevant articles published between 2001 and 2014 was performed. RESULTS: The search yielded a total of 882 articles, and after careful individual review for eligibility and relevancy, 9 peer-reviewed studies were included. A cause of the CBD dilation was found on average in 33% of cases and the most common causes were: CBD stone, chronic pancreatitis, and periampullary diverticulum. The overall CBD diameter was not associated with finding a causative lesion. Coexisting CBD and intrahepatic bile duct dilation, age, and jaundice were found to be indicators of pathologic lesions. Dilation of both the CBD and pancreatic duct was suggestive of pancreatic disease, especially pancreatic malignancy in the setting of obstructive jaundice. Follow-up was reported in 6 studies ranging from 6 to 85 months, and generally there was no change in the diagnosis. CONCLUSIONS: Incidentally found biliary tract dilatation can be a manifestation of significant biliary tract disease including malignancy. Long-term outcome is not well defined and further prospective studies examining the most cost-effective approach to evaluation are needed.
BMJ Open Gastroenterology · 2019 · 25 citations · open access
Practical strategies for pruritus management in the obeticholic acid-treated patient with PBC: proceedings from the 2018 expert panel
AbstractBACKGROUND AND AIMS: This article provides expert guidance on the management of pruritus symptoms in patients receiving obeticholic acid (OCA) as treatment for primary biliary cholangitis (PBC). PBC is a chronic, autoimmune cholestatic liver disease that affects intrahepatic bile ducts. If not adequately treated, PBC can lead to cholestasis and end-stage liver disease, which may require transplant. Timely treatment is therefore vital to patient health. Pruritus is a common symptom in patients with PBC. Additionally, the use of OCA to treat PBC can contribute to increased pruritus severity in some patients, adding to patient discomfort, decreasing patient quality of life (QoL), and potentially affecting patient adherence to OCA treatment. METHODS: In May 2018, a group of physician experts from the fields of gastroenterology, hepatology, and psychiatry met to discuss the management of pruritus in OCA-treated patients with PBC. Recognizing the importance of optimizing treatment for PBC, these experts developed recommendations for managing pruritus symptoms in the OCA-treated PBC patient based on their experience in clinical practice. RESULTS: These recommendations include a comprehensive list of management strategies (including over-the-counter, prescription, and alternative therapies), guidance on titration of OCA to minimize pruritus severity, and an algorithm that outlines a practical approach to follow up with patients receiving OCA, to better assess and manage pruritus symptoms. CONCLUSIONS: Pruritus associated with OCA therapy is dose dependent and often manageable, and with the proper education and tools, most pruritus cases can be effectively managed to minimize treatment discontinuation.
Afro-Egyptian Journal of Infectious and Endemic Diseases · 2022 · 0 citations · open access
Endoscopic Ultrasound at Crossroads in COVID - 19 era: a Multi-Center Global Study.
AbstractBackground and study aim: During COVID-19 pandemic most of non-emergency endoscopic procedures has been suspended. Endoscopic ultrasound (EUS) is important diagnostic and therapeutic procedure. This survey aimed to provide a rapid assessment of status of EUS during COVID-19 pandemic in different leading units of the world. Patients and Methods: Senior endoscopists from 10 different countries were invited to participate. Patient demographics, COVID-19 status, EUS indications as well as laboratory and radiology findings were reported. Pre-procedural preparation and post procedure complications were reported. Data were analyzed to reveal the effect of SARS-CoV-2 pandemic on different perspectives of EUS practice in the collaborating endoscopy units. Descriptive analysis was done by calculating percentages for categorical variables and mean± standard deviation for quantitative variables. Results: data of 316 patients from 11 countries were accrued. The mean (± SD) age of the patients in this study was 55.57±13.94 years. In this analysis 62.3% were laboratory confirmed SARS-Cov-2 negative while 8 patients were suspected and only 1 patient was laboratory confirmed positive for COVID -19. Daily performance of EUS was similar in before and during COVID-19 pandemic with an insignificant decrease of -1.1%. Emergent and urgent EUS was needed in 58 (14.4%) and 91 (28.8%) patients respectively. Pancreatic mass (27.8%),biliary dilatation (10.4%) formed major chunk of indications for procedure. Therapeutic outcomes were achieved with majority (40.8%). Conclusion: our data underscores the point of efforts of clinicians to provide the same level of care provided by EUS units despite the negative impact of COVID-19 pandemic.
[Interpretation of key points of the technical guidelines for clinical trials of drugs for the treatment of primary biliary cholangitis].
AbstractThere are limited drug options in the field of primary biliary cholangitis, so there is a great clinical need. In recent years, research and development of PBC treatment medications have been active domestically and internationally, and clinical trials have been conducted on multiple drugs with distinct targets. Therefore, on February 13, 2023, the State Drug Administration issued the "Technical Guidelines for Clinical Trials of Drugs for the Treatment of Primary Biliary Cholangitis" in order to guide and standardize the clinical trials of drugs for the treatment of PBC. This article briefly summarizes the key points of the guiding principles, focuses on the difficulties of clinical evaluation of drugs, discusses the key elements of clinical trials such as the selection of test populations and efficacy endpoints, and introduces the determination process through literature searches and expert discussion methods combined with reviewer experience and scientific considerations.
[Conversion therapy of biliary tract cancer from the perspective of tumor heterogeneity].
AbstractBiliary tract cancer is found in the middle and advanced stages mostly and patients will deprive surgical indications. Conversion therapy can make the stage of some patients down and thus make radical resection feasible. Biliary tract cancer is highly heterogeneous in clinical features, cell origin, histology, molecular biology and other aspects, resulting in a lack of specific and effective conversion therapy strategies. Currently, it is the important development direction to evaluate and classify different individual conditions and select individualized conversion therapy regimens. With the deepening of the research on the pathogenesis and the improvement of treatment protocols, the future conversion therapy will undoubtedly develop towards the direction of individualization and precision.
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.
