DeCure for Benign recurrent intrahepatic cholestasis type 2
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for benign recurrent intrahepatic cholestasis type 2 — 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 moduleBenign recurrent intrahepatic cholestasis type 2 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 benign recurrent intrahepatic cholestasis type 2 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
ATP binding cassette subfamily B member 11 (ABCB11) — ABCB11 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8PMJ · 2.81 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
A young patient with BRIC-2 showed almost complete absence of BSEP from the canalicular membrane of liver cells, with two BSEP mutations found: E186G (previously described in one BRIC-2 case) and V444A (linked to intrahepatic cholestasis of pregnancy). The authors concluded that compound heterozygosity reduces BSEP protein via instability or mis-targeting, causing reduced bile salt excretion and cholaemia. Only 70 cases of recurrent intrahepatic cholestasis had been reported by 1987; one patient followed for over 25 years showed no adverse physical consequences or histological deterioration on sequential liver biopsies, leading the authors to recommend a conservative approach to diagnosis and treatment.
An 11-year-old Saudi girl had three episodes of pruritus and jaundice at ages 4, 8, and 9, each lasting 5–8 weeks. Liver enzymes and serum bile acids rose during attacks and returned to normal between them. Cholestyramine therapy shortened the attacks. In a 2016 case, a BRIC-2 patient with refractory pruritus that did not respond to nasobiliary drainage improved rapidly with plasma separation and anion absorption therapy. A 2025 case report notes that BRIC is autosomal recessive with mutations in hepatocyte bile duct membrane proteins, most often homozygous; only 30% of cases have multiple heterozygous mutations. That report describes a patient with heterozygous mutations in a single gene and prominent symptoms, suggesting that multiple heterozygous mutations are not always required for severe clinical manifestations.
No controlled trials exist for BRIC-2. The evidence base remains limited to case reports and small case series. What is missing is systematic data on the natural history of BRIC-2 specifically (separate from BRIC-1), prospective studies of treatments such as cholestyramine or extracorporeal blood purification, and any trial that stratifies patients by genotype or BSEP expression level. Funding for a registry or for genotype-phenotype correlation studies would be needed before any treatment can be evaluated properly.
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 Clinical Gastroenterology · 2005 · 73 citations
Benign Recurrent Intrahepatic Cholestasis Associated With Mutations of the Bile Salt Export Pump
AbstractA young patient with recurrent attacks of intrahepatic cholestasis is described. On the basis of clinical presentation, laboratory findings and genetic analysis, the diagnosis of benign recurrent intrahepatic cholestasis type 2 (BRIC-2) was established. By the use of BSEP-specific antibodies, almost complete absence of BSEP from the canalicular membrane of liver cells was detected in the patient. Two different BSEP mutations were found. One mutation (E186G) had been described in one BRIC-2 case; the second mutation (V444A) is more frequent and has been linked to intrahepatic cholestasis of pregnancy. It is concluded that this form of compound heterozygosity of the BSEP gene reduces the amount of BSEP protein due to protein instability or mis-targeting, which is the underlying reason for reduced bile salt excretion and cholemia.
Postgraduate Medical Journal · 1987 · 16 citations · open access
Benign recurrent intrahepatic cholestasis--25 years of follow-up
AbstractOnly 70 cases of recurrent intrahepatic cholestasis have been reported in the literature since the original description of this entity in 1959. The benign nature of the disease has been questioned, some authors suggesting progression to biliary cirrhosis. We report our follow-up of one such patient for over 25 years with no adverse physical consequences or histological deterioration. Sequential liver biopsies were obtained during this period. A conservative approach to diagnosis and treatment is therefore indicated.
Annals of Tropical Paediatrics · 1999 · 9 citations
Benign recurrent intrahepatic cholestasis in a Saudi child
AbstractWe report a case of benign recurrent intrahepatic cholestasis (BRIC) in an 11-year-old Saudi girl who developed three episodes of pruritus and jaundice at the ages of 4, 8, and 9 years. These episodes were almost stereotypic and lasted 5-8 weeks. Although she had elevated liver enzymes and serum bile acids in her blood during the attacks, they returned to normal between attacks. Thorough investigation excluded other causes of liver disease and her recurrent attacks were shortened by cholestyramine therapy. A diagnosis of BRIC should be kept in mind in patients with cholestasis.
Zeitschrift für Gastroenterologie · 2016 · 0 citations
Extracorporeal blood purification improves nasobiliary drainage (NBD)-refractory pruritus in a BRIC type 2 patient
AbstractIntroduction: Benign recurrent intrahepatic cholestasis type 2 (BRIC2) is a rare genetic disease caused by mutations of the hepatobiliary transporter for bile salts (ABCB11). It is characterized by episodes of cholestatic itch and jaundice. Here we present a case of refractory BRIC type 2 who improved rapidly with plasma separation and anion absorption therapy.
Baltic Journal of CLINICAL MEDICINE and RESEARCH · 2025 · 0 citations · open access
Recurrent Hyperbilirubinemia: The Diagnostic Challenge of Benign Recurrent Intrahepatic Cholestasis
AbstractBenign recurrent intrahepatic cholestasis (BRIC) is an autosomal recessive disorder characterized by mutations in genes encoding hepatocyte bile duct membrane proteins, most often in a homozygous form; only 30 % of cases exhibit multiple heterozygous mutations. This case presents an unusual instance of BRIC with heterozygous mutations in a single gene encoding a hepatocyte bile duct membrane protein, accompanied by prominent clinical symptoms. Typically, multiple heterozygous mutations are thought to intensify clinical manifestations, but this case suggests otherwise. Keywords: benign recurrent intrahepatic cholestasis, conjugated hyperbilirubinemia
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.
