DeCure for Polycystic kidney disease 3 with or without polycystic liver disease
DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for polycystic kidney disease 3 with or without polycystic liver disease — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePolycystic kidney disease 3 with or without polycystic liver disease maps to a 3-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 kidney disease 3 with or without polycystic liver 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
In a cross-sectional study of 578 patients with polycystic liver disease, 35% underwent invasive therapy. A higher number of symptoms and every 10 years of diagnosis increased the likelihood of treatment by 40% (RR 1.4 for both, P < 0.001 and P = 0.03). The choice between liver transplantation and aspiration sclerotherapy depended on the treating centre (RR 0.7, P < 0.001 and RR 1.1, P = 0.03). No drug was evaluated in that study.
A 2019 review lists clinical trials of vasopressin V2 receptor antagonists (tolvaptan, liksivaptan), a multi-kinase inhibitor (tezevatinib), somatostatin analogues (lanreotide, octreotide), statins (pravastatin), mTOR inhibitors (everolimus, sirolimus), and metformin in patients with autosomal recessive and autosomal dominant polycystic kidney disease. The review does not report numerical outcomes, response rates, or survival data for any of these drugs.
A 2010 case report describes a 63-year-old man with polycystic kidney and liver disease whose enlarged liver compressed the inferior vena cava and right atrium, causing hypotension that required continuous venovenous haemodialysis and left lateral positioning. He underwent CT-guided aspiration of a dominant liver cyst and was started on octreotide as a temporary measure before combined liver and kidney transplantation. The report states that somatostatin analogues such as octreotide reduce liver volume in polycystic liver disease, but provides no quantitative data on the magnitude or duration of that reduction, and the patient received octreotide only as a bridge to transplant.
What is still missing are randomised controlled trials that report hard endpoints such as time to renal failure, need for transplantation, or survival for any drug in polycystic kidney disease. The existing evidence consists of small case series, reviews without numerical results, and centre-dependent surgical practice. No drug has been shown in a prospective trial to alter the natural history of the disease. Funding for adequately powered trials, clear patient stratification by genotype and disease stage, and standardised outcome measures are all lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Transplant International · 2016 · 16 citations · open access
Center is an important indicator for choice of invasive therapy in polycystic liver disease
AbstractPolycystic liver disease (PLD) is a rare genetic disorder with progressive cyst growth as the primary phenotype. Therapy consists of volume reduction through invasive surgical or radiological procedures. To understand the process of treatment decision, our aim was to identify factors that increased the likelihood of treatment. We performed a cross-sectional study using an international population of patients with PLD. We collected data on the following therapies: liver transplantation, resection, fenestration, and aspiration sclerotherapy. Data on the potential determinants, sex, center, autosomal dominant polycystic kidney disease (ADPKD), autosomal dominant polycystic liver disease (ADPLD), age at diagnosis, symptoms, and phenotype, were included. We corrected for follow-up time. We included 578 patients in our study, and 35% underwent invasive therapy. Multivariate regression analysis showed that number of symptoms and age at diagnosis of PLD increased the likelihood of treatment (respectively, RR: 1.4, P < 0.001 and RR = 1.4, P = 0.03). The choice for liver transplantation or aspiration sclerotherapy was center dependent (RR: 0.7, P < 0.001 and RR: 1.1, P = 0.03, respectively). The results of our international cross-sectional study suggest that a higher number of symptoms and every 10 years of PLD diagnosis increase the risk to undergo treatment by 40%. The choice to elect a particular modality is center dependent.
Rossiyskiy Vestnik Perinatologii i Pediatrii (Russian Bulletin of Perinatology and Pediatrics) · 2019 · 2 citations · open access
Treatment of autosomal recessive and autosomal dominant polycystic kidney disease
AbstractThe article reflects the genetic variants of polycystic kidney disease, describes the modern strategy for the treatment of polycystic kidney disease in children and adults. The authors present the results of clinical trials of vasopressin V2 receptor antagonists (tolvaptan, liksivaptan), a multi-kinase inhibitor (tezevatinib), somatostatin analogues (lankreotide, octreotide), statins (pravastatin), mTOR inhibitors (everolimus, sirolimus), metformin in patients with autosomal recessive and autosomal polycystic kidney disease. The authors discuss the factors determining the prognosis and outcome of these diseases.
The American Journal of Gastroenterology · 2010 · 0 citations
Polycystic Liver Disease Inducing Right Atrial Dysfunction: A Case Report
AbstractPurpose: Polycystic liver disease (PLD) may be sporadic or dominantly inherited. The occurrence is either an autosomal dominant polycystic kidney disease (ADPKD) in which the progressive development of renal cysts inevitably causes loss of renal function, or polycystic liver may be a sole manifestation. In addition to the cyst formation in multiple organs, this systemic disease is also characterized by abnormalities in the cardiovascular system. The purpose of this paper is to demonstrate a rare manifestation of mass effect associated with PLD. Methods: This is a retrospective case study of a 63-year-old male with adult polycystic kidney and liver disease, who presented to our institution with abdominal pain and flu-like symptoms in 2010. He was followed closely by several specialty teams throughout his hospital course which included the liver and kidney transplant teams. Similar case presentations in the literature were reviewed and integrated into our report. Results: The patient's hospital course was complicated by acute renal failure and E. cloace bacteremia causing severe sepsis with hypotension. However, after adequate infection control the patient remained significantly hypotensive, thus mandating daily CVVHD. The patient had to lie in the left lateral recumbent position to achieve a mean atrial pressure greater than 70 mm Hg. Further workup including CT and echocardiogram revealed the inferior vena cava and right atrium to be partially compressed by an enlarged polycystic liver parenchyma. As a temporary measure, he underwent CT-guided aspiration of the dominant liver cyst for temporary symptomatic relief. He was started on octreotide and expeditiously placed on a combined liver and kidney transplant list. Eleven days later, he successfully underwent combined orthotopic liver and kidney transplant from a deceased donor. Conclusion: There is substantial variation in presentation and size of liver cysts in polycystic liver disease, however it is rare to see symptomatic mass effect exclusive to the right atrium as seen in our patient. There are two additional case reports that demonstrate a similar presentation of cardiac compression. While the curative therapy to reduce the burden of liver volume in these patients is either resection or liver transplantation, the induction of octreotide is indicated in non-surgical candidates. Somatostatin analogues, such as octreotide, reduce liver volume in those with polycystic liver disease. Our case report is unique in that it demonstrates an abnormal presentation of a rare disease and reports the use of a drug that is currently under study for an alternative method of symptomatic relief prior to transplantation.
Revista Española de Enfermedades Digestivas · 2025 · 0 citations
Ductal Plate Malformation Revisited: biliary lesions from polycystic hepatorenal disease. An educational review.
AbstractPolycystic kidney diseases are linked to a myriad of hepatobiliary diseases. Patients with such diseases have a higher risk of admission. Clinical manifestations and complementary testing differ from healthy controls leading to suboptimal care. This review focuses on the different hepatobiliary diseases linked to polycystic kidney diseases, their diagnosis, clinical manifestations and management.
Oxford University Press eBooks · 2015 · 0 citations
Management of cystic liver disease
AbstractAbstract In a subset of autosomal dominant polycystic kidney disease patients, hepatic cysts dominate the clinical picture. These patients may develop polycystic liver disease, and enlargement of the liver leads to compression of adjacent abdominal and thoracic organs. The main risk factors for growth of liver cysts are female sex, exogenous oestrogen use, multiple pregnancies, and severity of renal disease. Treatment is only indicated in those with symptoms, and choice of treatment depends on total liver volume, size, and location of the liver cysts. Current radiological and surgical therapies include aspiration-sclerotherapy, fenestration, segmental hepatic resection, and liver transplantation. They all are palliative in nature and are partially effective and have non-negligible morbidity and mortality. Somatostatin analogues are still in development for polycystic liver disease.
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.
