DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for polycystic liver disease 1 — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePolycystic liver disease 1 maps to a 6-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 polycystic liver disease 1 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
Polycystic liver disease is a genetic disorder in which more than ten cysts form in the liver, either in isolation or together with polycystic kidney disease. Most patients are asymptomatic and require no intervention beyond reassurance and genetic counselling. In 2–5% of cases the disease causes disabling symptoms from the compressive effects of enlarged cysts, and can lead to malnutrition, liver decompensation, and death. The exact pathophysiology remains unclear, but ductal plate malformation, ciliary dysfunction, and changes in cholangiocyte proliferation and fluid secretion are involved.
No curative medical option exists. Somatostatin analogues have been shown in rodents and in humans to diminish liver volume, but a 2012 review states they have shown only minimal efficacy in human studies. A 2011 systematic review notes that the role of mTOR inhibitors is still under investigation. Conservative surgical approaches are only partially effective and do not change the natural course of the disease. Liver transplantation is the only treatment that can cure the condition, but it is limited by organ shortage.
The 2011 review found that abnormalities in cholangiocyte proliferation and enhanced fluid secretion are key factors in pathophysiology, and that somatostatin analogues reduce liver volume. The 2012 review confirms that somatostatin analogues hold promise but have shown minimal efficacy in human studies. The 2022 review states that somatostatin analogues hold promise in controlling disease progression, but that liver transplantation remains the only curative treatment.
What is still missing is a clear understanding of the exact pathophysiology, which limits rational drug design. No medical therapy has yet demonstrated a change in the natural history of the disease in a large, well-controlled trial. Patient stratification — distinguishing those with isolated polycystic liver disease from those with polycystic kidney disease — is rarely addressed in drug studies, and funding for rare-disease trials remains scarce.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Systematic review: the pathophysiology and management of polycystic liver disease
AbstractBACKGROUND: Polycystic liver diseases (PCLD) represent a group of genetic disorders in which cysts occur solely in the liver, or together with renal cysts. Most of the patients with PCLD are asymptomatic, however, in some patients, expansion of liver cysts causes invalidating abdominal symptoms. AIM: To provide a systemic review on the pathophysiology and management of PCLD. METHODS: A PubMed search was undertaken to identify relevant literature using search terms including polycystic liver disease, pathophysiology, surgical and medical management. RESULTS: The most common complication in patients with PCLD is extensive hepatomegaly, which may lead to malnutrition and can be lethal. Conservative surgical approaches are only partially effective and do not change the natural course of the disease. Liver transplantation has been successfully performed in PCLD, however, in an era of organ shortage, medical management needs to be evaluated. A better understanding of the pathophysiology and the availability of animal models have already identified promising drugs. Abnormalities in cholangiocyte proliferation/apoptosis and enhanced fluid secretion are key factors in the pathophysiology. It has been demonstrated in rodents and in humans that somatostatin analogues diminish liver volume. The role of the inhibitors of the mammalian target of rapamycin (mTOR) in the management of PCLD is still under investigation. CONCLUSIONS: The exact pathophysiology of polycystic liver disease still remains unclear. In symptomatic patients, none of the currently available surgical options except liver transplantation have been shown to change the natural course of the disease. The use of somatostatin analogues has been shown to diminish liver volume.
Annals of Hepatology · 2012 · 74 citations · open access
Polycystic liver disease: a clinical review
AbstractPolycystic liver disease rarely occurs in isolation as part of autosomal dominant polycystic liver disease, but more commonly, it exists as an extra-renal manifestation of autosomal dominant polycystic kidney disease. The pathogenesis of polycystic liver disease involves defects in the primary cilium of the cholangiocyte, with genetic mutations that impair key proteins integral to the complex functioning of cilia. While most patients are asymptomatic and require no intervention aside from reassurance and genetic counseling, in a minority of patients, polycystic liver disease creates a myriad of symptoms from the compressive effects of enlarged cysts, and can even cause malnutrition and liver decompensation in the severest of cases. In patients with symptomatic disease, a variety of interventional radiology or surgical techniques can be considered, including aspiration with sclerotherapy of a dominant cyst, fenestration, segmental hepatic resection, and even liver transplantation. Although there are no curative medical options for polycystic liver disease, somatostatin analogs hold promise and have shown minimal efficacy in human studies. However, further research is needed to develop more efficacious medical treatments.
Hepatic Medicine Evidence and Research · 2022 · 27 citations · open access
Polycystic Liver Disease: Pathophysiology, Diagnosis and Treatment
AbstractPolycystic liver disease (PLD) is a clinical condition characterized by the presence of more than 10 cysts in the liver. It is a rare disease Of genetic etiology that presents as an isolated disease or assoc\iated with polycystic kidney disease. Ductal plate malformation, ciliary dysfunction, and changes in cell signaling are the main factors involved in its pathogenesis. Most patients with PLD are asymptomatic, but in 2-5% of cases the disease has disabling symptoms and a significant reduction in quality of life. The diagnosis is based on family history of hepatic and/or renal polycystic disease, clinical manifestations, patient age, and polycystic liver phenotype shown on imaging examinations. PLD treatment has evolved considerably in the last decades. Somatostatin analogues hold promise in controlling disease progression, but liver transplantation remains a unique curative treatment modality.
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.
