DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Alagille syndrome — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAlagille syndrome maps to a 5-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 alagille syndrome 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
notch receptor 2 (NOTCH2) — NOTCH2 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 bgcdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5MWB · 1.86 Å · ligand beta-D-glucopyranose (BGC). Experimental structure, not a prediction.
What the evidence adds up to
Alagille syndrome is a highly variable autosomal dominant disorder caused primarily by mutations in the Notch signalling pathway ligand JAGGED1. It affects the liver, heart, eyes, face, skeleton, kidneys, and vascular system. The liver disease in particular requires an appreciation of the natural history and evolution of profound cholestasis. The most frequent clinical manifestations are neonatal jaundice, chronic cholestasis, and cardiac, ocular and skeletal malformations associated with characteristic facial features. Significant intrafamilial variability is reported.
A retrospective analysis of insurance claims from October 2015 to December 2019 identified 171 commercially insured and 215 Medicaid-insured children with Alagille syndrome. Annually, commercially insured patients averaged 31 medical visits (range 1.5–237) and Medicaid-insured patients averaged 48 medical visits (range 0.7–690). Outpatient visits, mostly lab/imaging and primary care, were the most common (commercially insured: 21 per year, range 0.0–183; Medicaid-insured: 26 per year, range 0.0–609). Inpatient visits were the highest driver of costs in both populations.
An atypical adult case has been reported: a Japanese patient diagnosed as an infant by liver biopsy required haemodialysis at age 27 but could not have an arteriovenous fistula created because his peripheral blood vessels were too narrow. He also had recurrent brain infarction due to cerebral vascular stenosis. The authors note that Alagille syndrome is generally recognised as a paediatric hepatic disease but can present with renal involvement and vascular abnormalities in adults.
Although the molecular basis of Alagille syndrome is well defined, no specific targeted therapy exists. The medical management remains complex and controversial. What is still missing is any therapy that addresses the underlying Notch pathway defect, prospective data on how to stratify patients by organ involvement, and funding for clinical trials that go beyond descriptive natural history 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.
Journal of Pediatric Gastroenterology and Nutrition · 2010 · 74 citations
Medical Management of Alagille Syndrome
AbstractAlagille syndrome is a highly variable, autosomal dominant disorder that affects the liver, heart, eyes, face, skeleton, kidneys, and vascular system. Much has been learned about the genetics of this disorder, which is caused primarily by mutations in the Notch signaling pathway ligand JAGGED1; however, the medical management of this condition is complex and continues to generate controversy. The significant variability of organ involvement requires the managing physician to have an understanding of the breadth and interplay of the variable manifestations. Furthermore, the liver disease in particular requires an appreciation of the natural history and evolution of the profound cholestasis.
The Journal of Pediatrics · 2022 · 7 citations · open access
Health Care Resource Utilization by Patients with Alagille Syndrome
AbstractOBJECTIVE: To assess and characterize health care resource utilization (HRU) in children with the rare, genetic, multisystem disorder, Alagille syndrome. STUDY DESIGN: This retrospective analysis reviewed commercially insured and Medicaid-insured claims from October 1, 2015 to December 31, 2019 to assess HRU in patients with Alagille syndrome. As there is no specific International Classification ofDiseases-10 code for Alagille syndrome, patients were identified using the following algorithm: ≥1 claim with diagnosis code Q44.7 (other congenital malformations of the liver); <18 years of age, with no history of biliary atresia (International Classification ofDiseases-10 code: Q44.2); and ≥6 months of insurance eligibility prior to diagnosis. HRU was summarized per patient per year over all available claims postdiagnosis. RESULTS: A total of 171 commercially insured and 215 Medicaid-insured patients with Alagille syndrome were available for analysis. Annually, commercially insured and Medicaid-insured patients averaged 31 medical visits (range, 1.5-237) and 48 medical visits (range, 0.7-690), respectively. The most common visits were outpatient with the majority encompassing lab/imaging and primary care visits (commercially insured: 21 [range, 0.0-183]; Medicaid-insured: 26 [range, 0.0-609]). Inpatient visits were the highest driver of costs in both the commercial and Medicaid populations. CONCLUSIONS: Patients with Alagille syndrome have a substantial HRU burden driven largely by numerous outpatient visits and costly inpatient stays. Given the complexity and variability of Alagille syndrome presentation, patients may benefit from multidisciplinary and subspecialized care.
Internal Medicine · 2020 · 6 citations · open access
An Adult Patient with Alagille Syndrome Showing Mainly Renal Failure and Vascular Abnormality without Liver Manifestation
AbstractAlagille syndrome is an inherited multisystemic disorder. We herein report an atypical case of a Japanese adult patient with Alagille syndrome. He had been diagnosed with Alagille syndrome as an infant based on a liver biopsy. At 27 years of age, he needed to start hemodialysis therapy, but an arteriovenous fistula was not created because his peripheral blood vessels were too narrow. He also had a recurrent brain infarction due to cerebral vascular stenosis. Alagille syndrome is generally recognized as a pediatric hepatic disease, but general physicians should be aware of its potential existence with renal involvement and vascular abnormalities.
European Society of Radiology · 2020 · 0 citations · open access
Imaging features of Alagille Syndrome: focus on a rare but important condition.
AbstractPoster: ECR 2020 / C-04423 / Imaging features of Alagille Syndrome: focus on a rare but important condition. by: M. Milazzo 1, A. Di Piazza1, C. Cannataci2, V. Carollo3, S. Caruso4, G. Marrone1, G. Gentile1, R. Miraglia5; 1Palermo/IT, 2Msida/MT, 3Palermo (PA)/IT, 4Palermo (PA), italy/IT, 5Palermo /IT
AbstractAlagille syndrome is a rare disorder with low physician awareness. It affects multiple organs and thus patient management involves several medical specialties. It is an autosomal dominant disorder with significant intrafamilial variability. The most frequent clinical manifestations are neonatal jaundice, chronic cholestasis as well as cardiac, ocular and skeletal malformations associated with characteristic facial features. Inherited mutations affect the Notch pathway. Although the molecular basis of Alagille syndrome is well defined, no specific targeted therapy exists.
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.
