DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for biliary atresia — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBiliary atresia maps to a 4-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 atresia 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
sodium voltage-gated channel alpha subunit 9 (SCN9A) — SCN9A 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…
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RCSB Protein Data Bank · entry 7W9K · 2.2 Å · ligand O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine (P5S). Experimental structure, not a prediction.
What the evidence adds up to
Biliary atresia remains a disease of unknown cause. Whole-genome association studies have identified four predisposition loci with four different genes potentially involved, but no pathogenic variations in those genes have been found in patients. The inheritance is not Mendelian, and the disease is most likely related to complex traits. Noncoding and epigenetic factors have been proposed as alternatives to classic genetic alterations. Despite decades of research, the cause remains enigmatic.
In a rhesus rotavirus-induced mouse model of biliary atresia, the Notch signalling target gene Hes1 was examined. Immunohistochemical staining showed changes in biliary epithelial cell morphology in both patients and the mouse model. Administration of Hes1 siRNA in a 3D culture system blocked the formation of duct-like structures, leaving cells in an immature state. The authors concluded that Hes1 might contribute to the maturation and structural organisation of biliary epithelial cells.
Clinically, all therapeutic attempts remain symptomatic. Stool colour cards have been shown to be an accurate screening tool for early diagnosis. Postoperative corticosteroid therapy remains an area of debate without definitive data. Early postoperative testing of serum bilirubin levels and hepatobiliary scintigraphy show strong correlation with long-term outcomes. The overall survival rate of patients has increased in recent decades, mainly due to improved outcomes after liver transplantation. At the end stage, the majority of patients still need organ replacement.
What is still missing is a confirmed genetic or infectious cause that could guide targeted therapy. No pathogenic gene variants have been found in patients despite identified loci. The role of Hes1 in human biliary atresia has not been tested in a clinical trial. There are no randomised data on postoperative corticosteroids. Multicentre collaboration in basic science and clinical research has begun but has not yet delivered a disease-modifying treatment.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Current Opinion in Gastroenterology · 2018 · 44 citations
Genetics in biliary atresia
AbstractPURPOSE OF REVIEW: Biliary atresia is a poorly understood deadly disease. Genetic predisposition factors are suspected albeit not firmly established. This review summarizes recent evidence of genetic alterations in biliary atresia. RECENT FINDINGS: Whole-genome association studies in biliary atresia patients identified four distinct predisposition loci with four different genes potentially involved in the disease occurrence. Variations in these genes were searched for, but none were found in patients with biliary atresia suggesting complex mechanisms. SUMMARY: Despite decades since its description and decades of intensive researches, cause of biliary atresia disease remains enigmatic. The inheritance of biliary atresia is not Mendelian. Genetic predisposition factor is one of the explored fields to explain biliary atresia pathogenicity. Biliary atresia has been associated with several inborn syndromes, chromosome anomalies, and gene polymorphisms in specific populations. Four predisposition loci encompassing genes relevant to the disease have been identified, but no pathogenic variations were found in biliary atresia patients. Few reported cases of isolated biliary atresia manifestation in the context of known genetic diseases suggest coincidental findings. Alternatives to classic genetic alterations are proposed to explain genetic predisposition in biliary atresia including noncoding and epigenetic factors. Biliary atresia is most likely related to complex traits making its genetic exploration challenging.
Current Opinion in Pediatrics · 2008 · 12 citations
Advances in the understanding and treatment of biliary atresia
AbstractPURPOSE OF REVIEW: The purpose of this study is to review both the basic science and clinical advancements in the last 12 months that have furthered our understanding of biliary atresia. RECENT FINDINGS: Early diagnosis and further understanding of the disease process may be the next major step in advancement. Stool color cards have been shown to be an accurate screening tool. Basic science developments have focused on defects in morphogenesis, immunologic dysregulation, and viral infection as the major theories of causes. There have been initial reports of minimally invasive approaches to hepatic portoenterostomy but there has been little comparative study. Postoperative corticosteroid therapy remains an area of debate without definitive data. Early postoperative testing of serum bilirubin levels and hepatobiliary scintigraphy are showing strong correlation with long-term outcomes. The comparison of regions with decentralization policies compared with those with central referral policies is providing a good forum to monitor real-time outcome data. SUMMARY: Biliary atresia continues to represent a major challenge with many unanswered questions. The establishment of multicentered collaboration in both basic science and clinical research interests has been an important step in improving outcomes for this disease.
European Journal of Pediatric Surgery · 2003 · 10 citations
What's New in Biliary Atresia?
AbstractThe main problem with biliary atresia (BA) is three-fold. Early diagnosis and timely therapy is mandatory in this rare and life-threatening disease. In as much as the aetiology of BA is unknown, all therapeutic attempts are still symptomatically orientated and finally, at the end-stage of the disease, the majority of the patients need organ replacement. Due to promising interdisciplinary cooperation and improved outcomes after liver transplantation, the overall survival rate of patients with BA increased remarkably during the last decades. Additionally, every effort was made in clinical and basic research to obtain a better understanding of the disease and its clinical course. Nevertheless, the nature of biliary atresia still remains unclear and therapeutic options are unsatisfactory. Numerous papers about BA have appeared, reflecting clinical and scientific activity. Considering recent publications and prospective activities, in the following we will summarise what is new in biliary atresia.
World Journal of Gastroenterology · 2018 · 8 citations · open access
Downregulation of Hes1 expression in experimental biliary atresia and its effects on bile duct structure
AbstractAIM: To analyze the expression and function of the Notch signaling target gene Hes1 in a rhesus rotavirus-induced mouse biliary atresia model. METHODS: The morphologies of biliary epithelial cells in biliary atresia patients and in a mouse model were examined by immunohistochemical staining. Then, the differential expression of Notch signaling pathway-related molecules was investigated. Further, the effects of the siRNA-mediated inhibition of Hes1 expression were examined using a biliary epithelial cell 3D culture system. RESULTS: cells and the formation of a duct-like structure. The administration of Hes1 siRNA blocked this process. As a result, the cells remained in an immature state, and no duct-like structure was observed. CONCLUSION: Our data indicated that Hes1 might contribute to the maturation and the cellular structure organization of biliary epithelial cells, which provides new insight into understanding the pathology of biliary atresia.
Effect of gene regulation in pathogenesis of biliary atresia
AbstractBiliary atresia (BA) is a common neonatal liver disease characterized by inflammation and fibrosis of the extrahepatic biliary ducts, leading to cholestasis and biliary cirrhosis.It is also a severe liver disease in infants.The pathogenesis of BA is associated with multiple genes and gene polymorphism, virus infections, epigenetic, immune abnormalities, and so on.With the development of genetic technology, it provides a new method to determine the susceptibility genes in BA.Now, more and more doctors pay attention to the change and regulation of genes in BA.
Key words:
Biliary atresia; Gene; Child
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.
