DeCure for Cryptosporidiosis-chronic cholangitis-liver disease syndrome
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for cryptosporidiosis-chronic cholangitis-liver disease syndrome — 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 moduleCryptosporidiosis-chronic cholangitis-liver disease syndrome 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 cryptosporidiosis-chronic cholangitis-liver disease 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
interleukin 21 receptor (IL21R) — IL21R 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 +drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4NZD · 2.75 Å · ligand L(+)-TARTARIC ACID (TLA). Experimental structure, not a prediction.
What the evidence adds up to
In a 2007 case report, a liver transplant patient with Cryptosporidium-associated sclerosing cholangitis improved on treatment with azithromycin and paromomycin. This is a single case, not a trial. A 2020 retrospective review of six paediatric liver transplant recipients with cryptosporidiosis found that infection led to hospitalisation in half of the patients, biopsy-proven rejection in four of six, and biliary tree abnormalities resembling sclerosing cholangitis in three. Three of the four patients with rejection developed rejection that was recalcitrant to intravenous steroid treatment. One patient with biliary changes required repeated biliary drain placement and showed advancing fibrotic allograft changes. The authors advocate for awareness but report no specific drug regimen that prevented these complications.
A 2003 study of 28 patients with primary immunodeficiencies (13 with CD40 ligand deficiency, 10 with undefined combined immunodeficiency, 2 with MHC II deficiency, 3 with other defects) used PCR to detect Cryptosporidium in stool, bile, and liver tissue. Among 25 patients tested prospectively, PCR detected the organism in 12 who were microscopy-negative; only 3 of those 12 had a known history of infection. Five of the 12 had sclerosing cholangitis. Nine of the PCR-positive patients subsequently underwent bone marrow transplantation, and five developed acute post-transplant diarrhoea and cholangiopathy with Cryptosporidium excretion. Among 13 PCR-negative patients, 3 had cholangiopathy (sclerosing cholangitis in 1, minor changes in 2); 4 underwent BMT and none developed cryptosporidiosis. In 3 patients studied only after developing post-BMT cholangiopathy and diarrhoea, PCR but not microscopy detected Cryptosporidium. Genotyping showed multiple Cryptosporidium types in about one-third of positive cases.
Across these studies, no controlled trial of any drug for cryptosporidiosis-chronic cholangitis-liver disease syndrome exists. The 2007 case used azithromycin and paromomycin, but the 2020 series does not report a consistent effective regimen, and the 2003 study focuses on detection, not treatment. What is missing is a prospective trial that stratifies patients by immune defect and biliary status, tests a defined antimicrobial regimen with adequate follow-up for rejection and biliary fibrosis, and is funded to enrol enough transplant and immunodeficiency patients to yield interpretable results.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
<i>Cryptosporidium parvum</i>‐associated sclerosing cholangitis in a liver transplant patient
AbstractCryptosporidium parvum causes severe long-standing diarrhea in immunocompromised patients. Sclerosing cholangitis caused by C. parvum is a rare complication in transplant recipients. We report herein the presentation of Cryptosporidium-associated cholangitis in an adult liver transplant patient diagnosed by liver biopsy. The patient improved on treatment with azithromycin and paromomycin.
Complications of Cryptosporidium infection after pediatric liver transplantation: Diarrhea, rejection, and biliary disease
AbstractBACKGROUND: Cryptosporidium enteritis can be devastating in the immunocompromised host. In pediatric liver transplant recipients, infection may be complicated by prolonged carriage of the parasite, rejection, and biliary tree damage and fibrosis. Herein, we report on six patients and their long-term outcomes following cryptosporidiosis. METHODS: We reviewed all cases of cryptosporidiosis in a pediatric liver transplant population over a 17-year period at a single center. Six patients with infection were identified, and their outcomes were analyzed. RESULTS: Infection was associated with significant diarrhea and dehydration in all cases, and led to hospitalization in one-half of patients. Four of the six patients developed biopsy-proven rejection following infection, with three of those patients developing rejection that was recalcitrant to intravenous steroid treatment. Additionally, three patients developed biliary tree abnormalities with similarity to sclerosing cholangitis. In one patient, those biliary changes led to repeated need for biliary drain placement and advancing fibrotic liver allograft changes. CONCLUSIONS: Cryptosporidiosis in pediatric liver transplant recipients may lead to significant complications, including recalcitrant episodes of rejection and detrimental biliary tree changes. We advocate for increased awareness of this cause of diarrheal disease and the allograft injuries that may accompany infection.
The Pediatric Infectious Disease Journal · 2003 · 1 citations
AbstractBackground. Patients with deficient cell-mediated immunity are prone to chronic biliary tract infection with Cryptosporidium, which can lead to the development of sclerosing cholangitis and acute cryptosporidiosis after bone marrow transplantation (BMT). The organism is very difficult to detect during asymptomatic periods. Methods. PCR techniques were compared with standard microscopy for detecting the organism in such patients. Amplification targets were two fragments of the 18S ribosomal RNA gene (unnested) and part of the Cryptosporidium oocyst wall protein gene (nested and unnested). Twenty eight-patients with primary immunodeficiencies were studied including: CD40 ligand deficiency (13); undefined combined immunodeficiency (10); major histocompatibility complex II deficiency (2); and other defects (3). Samples analyzed included stool, bile and liver tissue. Results. Of 25 patients tested prospectively, Cryptosporidium could be detected by PCR but not by microscopy in 12, only 3 of whom had a known history of infection. Five of this group had sclerosing cholangitis. Nine of the PCR-positive patients subsequently underwent BMT and 5 developed acute posttransplant diarrhea and cholangiopathy associated with Cryptosporidium excretion. Of the 13 PCR-negative patients, 3 had cholangiopathy (sclerosing cholangitis in 1 and minor changes in 2). Four of these underwent BMT and none developed cryptosporidiosis. In 3 patients, studied only after developing post-BMT cholangiopathy and diarrhea, Cryptosporidium was detected by PCR but not by microscopy. Genotyping and sequencing showed multiple types of Cryptosporidium in approximately one-third of positive cases. Conclusions. These results indicate that PCR-based procedures are more sensitive than microscopy for detecting Cryptosporidium in patients with immunodeficiencies.
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.
