DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Caroli Disease — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCaroli Disease maps to a 1-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 caroli 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
polycystin 1, transient receptor potential channel interacting (PKD1) — PKD1 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 1rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8ZKH · 2.3 Å · ligand (1R)-2-{[(S)-{[(2S)-2,3-dihydroxypropyl]oxy}(hydroxy)phosphoryl]oxy}-1-[(hexadecanoyloxy)methyl]ethyl
(9Z)-octadec-9-enoate (PGW). Experimental structure, not a prediction.
What the evidence adds up to
Whole exome sequencing of one Chinese twin with Caroli disease identified a compound heterozygous genotype in PKHD1: a missense mutation c.2507T>C (p.Val836Ala) and a nonsense mutation c.2341C>T (p.Arg781*). This genotype co-segregated with affected family members and was absent in 200 normal chromosomes. The authors concluded that exome sequencing can be useful for diagnosis and that the finding expands the known PKHD1 mutation spectrum associated with Caroli disease. No treatment or outcome data beyond genetic segregation were reported.
A 2024 case report stated that WDR19 gene mutations can present as Caroli disease or Caroli syndrome, and recommended whole exome sequencing for definitive diagnosis of liver diseases of unknown etiology. No patient numbers, survival data, or response rates were given.
A 2023 case report described one Caroli disease patient in whom 1.5% meglumine sodium succinate 500 ml IV once daily was used for courses of 5 and 8 days. The authors claimed the drug reduced intoxication syndrome and length of hospital stay, and improved quality of life, attributing this to an antihypoxic mechanism. The report involved a single patient, with no control group, no blinding, and no quantitative outcomes such as survival or objective response rates.
No randomised trials, no controlled studies, and no replicated findings exist for any drug in Caroli disease. What is missing is any prospective trial design, any patient stratification by genotype (PKHD1 versus WDR19), and any funding for a systematic investigation of drug repurposing in this rare disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PLoS ONE · 2014 · 21 citations · open access
Whole Exome Sequencing Identifies Recessive PKHD1 Mutations in a Chinese Twin Family with Caroli Disease
AbstractBACKGROUND: Mutations in PKHD1 cause autosomal recessive Caroli disease, which is a rare congenital disorder involving cystic dilatation of the intrahepatic bile ducts. However, the mutational spectrum of PKHD1 and the phenotype-genotype correlations have not yet been fully established. METHODS: Whole exome sequencing (WES) was performed on one twin sample with Caroli disease from a Chinese family from Shandong province. Routine Sanger sequencing was used to validate the WES and to carry out segregation studies. We also described the PKHD1 mutation associated with the genotype-phenotype of this twin. RESULTS: A combination of WES and Sanger sequencing revealed the genetic defect to be a novel compound heterozygous genotype in PKHD1, including the missense mutation c.2507 T>C, predicted to cause a valine to alanine substitution at codon 836 (c.2507T>C, p.Val836Ala), and the nonsense mutation c.2341C>T, which is predicted to result in an arginine to stop codon at codon 781 (c.2341C>T, p.Arg781*). This compound heterozygous genotype co-segregates with the Caroli disease-affected pedigree members, but is absent in 200 normal chromosomes. CONCLUSIONS: Our findings indicate exome sequencing can be useful in the diagnosis of Caroli disease patients and associate a compound heterozygous genotype in PKHD1 with Caroli disease, which further increases our understanding of the mutation spectrum of PKHD1 in association with Caroli disease.
Translational Pediatrics · 2024 · 5 citations · open access
A case report of intrahepatic bile duct dilatation caused by WDR19 gene mutation and presented as Caroli syndrome
AbstractBackground: gene mutations may contribute to extrarenal phenotypes such as Caroli disease or syndrome. Case Description: gene. Conclusions: gene can manifest as Caroli disease or Caroli syndrome. For the definite diagnosis of liver diseases of unknown etiology, whole exome sequencing may be more conducive.
Pirogov Russian Journal of Surgery · 2023 · 1 citations
Caroli disease: optimizing the choice of surgical strategy using 3D modeling, 3D printing and therapy
AbstractA patient with Caroli disease is described. The authors used 3D modeling and 3D printing when choosing surgical strategy. Advisability of 1.5% meglumine sodium succinate 500 ml IV once a day (courses for 5 and 8 days) is justified. Thanks to antihypoxic mechanism, this drug reduced intoxication syndrome and length of hospital-stay, as well as improved quality of life.
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.
