DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for atypical hemolytic-uremic syndrome — screening already-approved drugs against its 18-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleAtypical hemolytic-uremic syndrome maps to a 18-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 atypical hemolytic-uremic 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
hemoglobin subunit beta (HBB) — HBB 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 hemdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1DXT · 1.7 Å · ligand PROTOPORPHYRIN IX CONTAINING FE (HEM). Experimental structure, not a prediction.
What the evidence adds up to
The term atypical haemolytic uremic syndrome has been used since the mid-1970s to describe familial or sporadic forms of the disease, as opposed to the epidemic, typical form. Over time it has come to refer to anything that is not Shiga toxin-associated haemolytic uremic syndrome, covering a heterogeneous group of diseases of disparate causes. A 2024 working group of specialty-specific experts convened by the National Kidney Foundation used a Delphi approach to review the validity of this broad term in an era of targeted therapeutics, noting that the current nomenclature makes defining disease-specific natural history and targeted treatment approaches challenging.
A 2023 set of recommendations from a Scientific Committee of five experts, based on a literature review and validated through an online questionnaire and a second meeting, states that patients with confirmed or clear suspicion of atypical haemolytic uremic syndrome should be treated with C5 inhibitors within 24 hours of diagnosis or suspicion. Treatment monitoring and decisions to interrupt therapy should be individualised according to risk of relapse and each patient’s evolution. The committee recommends treatment for at least 6–12 months for cases with a genetic variant or associated with pregnancy; for de novo cases associated with kidney transplant until renal function recovers and genetic variants are ruled out; for cases associated with malignant hypertension until genetic variants are ruled out; and for cases associated with non-kidney transplant, autoimmune diseases, infection, or drug induction until the thrombotic microangiopathy is resolved. Patients with a high risk of relapse should be treated for longer than 6–12 months.
A 2022 observational study from Hyderabad describes haemolytic uremic syndrome as a rare, life-threatening disorder affecting children worldwide and causing acute kidney injury, characterised by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury. The study notes that haemolytic uremic syndrome without thrombocytopenia has been observed, termed partial HUS, but its real frequency and outcome are unknown. The report presents routine laboratory and molecular diagnostic findings from a single known case of atypical haemolytic uremic syndrome.
What is still missing is a precise, universally accepted disease definition that separates distinct causes within the current broad category, which would allow disease-specific natural history studies and targeted treatment trials. The 2023 recommendations are expert opinion, not a randomised trial, and the 2022 study is a single case. No large prospective data exist to confirm whether the proposed treatment durations and interruption rules improve long-term outcomes, and no validated biomarkers exist to stratify patients by relapse risk.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
New England Journal of Medicine · 2009 · 547 citations · open access
Thrombomodulin Mutations in Atypical Hemolytic–Uremic Syndrome
AbstractBACKGROUND: The hemolytic-uremic syndrome consists of the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal failure. The common form of the syndrome is triggered by infection with Shiga toxin-producing bacteria and has a favorable outcome. The less common form of the syndrome, called atypical hemolytic-uremic syndrome, accounts for about 10% of cases, and patients with this form of the syndrome have a poor prognosis. Approximately half of the patients with atypical hemolytic-uremic syndrome have mutations in genes that regulate the complement system. Genetic factors in the remaining cases are unknown. We studied the role of thrombomodulin, an endothelial glycoprotein with anticoagulant, antiinflammatory, and cytoprotective properties, in atypical hemolytic-uremic syndrome. METHODS: We sequenced the entire thrombomodulin gene (THBD) in 152 patients with atypical hemolytic-uremic syndrome and in 380 controls. Using purified proteins and cell-expression systems, we investigated whether thrombomodulin regulates the complement system, and we characterized the mechanisms. We evaluated the effects of thrombomodulin missense mutations associated with atypical hemolytic-uremic syndrome on complement activation by expressing thrombomodulin variants in cultured cells. RESULTS: Of 152 patients with atypical hemolytic-uremic syndrome, 7 unrelated patients had six different heterozygous missense THBD mutations. In vitro, thrombomodulin binds to C3b and factor H (CFH) and negatively regulates complement by accelerating factor I-mediated inactivation of C3b in the presence of cofactors, CFH or C4b binding protein. By promoting activation of the plasma procarboxypeptidase B, thrombomodulin also accelerates the inactivation of anaphylatoxins C3a and C5a. Cultured cells expressing thrombomodulin variants associated with atypical hemolytic-uremic syndrome had diminished capacity to inactivate C3b and to activate procarboxypeptidase B and were thus less protected from activated complement. CONCLUSIONS: Mutations that impair the function of thrombomodulin occur in about 5% of patients with atypical hemolytic-uremic syndrome.
Kidney International · 2024 · 34 citations · open access
An expert discussion on the atypical hemolytic uremic syndrome nomenclature—identifying a road map to precision: a report of a National Kidney Foundation Working Group
AbstractThe term atypical hemolytic uremic syndrome has been in use since the mid-1970s. It was initially used to describe the familial or sporadic form of hemolytic uremic syndrome as opposed to the epidemic, typical form of the disease. Over time, the atypical hemolytic uremic syndrome term has evolved into being used to refer to anything that is not Shiga toxin-associated hemolytic uremic syndrome. The term describes a heterogeneous group of diseases of disparate causes, a circumstance that makes defining disease-specific natural history and/or targeted treatment approaches challenging. A working group of specialty-specific experts in the thrombotic microangiopathies was convened to review the validity of this broad term in an era of swiftly advancing science and targeted therapeutics. A Delphi approach was used to define and interrogate some of the key issues related to the atypical hemolytic uremic syndrome nomenclature.
Data_Sheet_1_Recommendations for the individualised management of atypical hemolytic uremic syndrome in adults.docx
AbstractBackground Despite significant advances in therapeutic management of atypical hemolytic uremic syndrome (aHUS), guidelines are not timely updated and achieving a consensus on management recommendations remains a topic of ongoing discussion. Methods A Scientific Committee with five experts was set up. A literature review was conducted and publications addressing the classification of aHUS, patient profiles and therapeutic approach were selected. Recommendations were proposed at an initial meeting, evaluated through an online questionnaire and validated during a second meeting. Results Patients with confirmed or clear suspicion of aHUS should be treated with C5 inhibitors within 24 h of the diagnosis or suspicion of aHUS. Treatment monitoring and the decision to interrupt treatment should be individualised according to the risk of relapse and each patient’s evolution. aHUS with a genetic variant or associated with pregnancy should be treated for at least 6–12 months; de novo aHUS associated with kidney transplant until renal function is recovered and genetic variants are ruled out; aHUS associated with malignant hypertension until genetic variants are ruled out; aHUS associated with non-kidney transplant, autoimmune diseases, infection-or drug-induced until the thrombotic microangiopathy is resolved. Patients with a high risk of relapse should be treated for longer than 6–12 months. Conclusion These recommendations provides physicians who are not familiar with the disease with recommendations for the management of aHUS in adults. The experts who participated advocate early treatment, maintenance for at least 6–12 months and treatment interruption guided by genetic background, trigger factors, risk of relapse and evolution.
INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH · 2022 · 0 citations
ATYPICAL HEMOLYTIC UREMIC SYNDROME-AN OBSERVATIONAL STUDY ON ROUTINE LABORATORY AND GENETIC WORKUP.
AbstractHemolytic Uremic syndrome(HUS) is a rare,life threatening disorder,affecting children world wide and causing acute kidney injury.It is characterized by the triad of thrombotic microangiopathy, thrombocytopenia, and acute kidney injury. HUS without thrombocytopenia has been observed, termed as partial HUS. Its real frequency and outcome are unknown. Asimilar case of atypical hemolytic uremic syndrome presented to the diagnostic lab,Helping Hand Foundation,Hyderabad,for routine laboratory investigations.The investigations were performed and the data was collected for the study.The aim of this study is to provide the ndings of rountine laboratory investigations and molecular diagnostics, of a known case of atypical Hemolytic uremic syndrome.
Romanian Journal of Pediatrics · 2017 · 0 citations · open access
HEMOLYTIC UREMIC SYNDROME – A CASE PRESENTATION
AbstractThe presentation aims to illustrate in a didactic manner the clinical aspects, laboratory findings and the diagnostic steps in a case of hemolytic uremic syndrome (HUS), also pointing out the importance of differential diagnosis for the triad consisting of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. The clinician's approach regarding the prognostic factors is also depicted, alongside the hallmarks concerning the treatment of HUS, the aspects of acute kidney injury monitoring and the need for a long term follow-up of HUS patients.
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.
