DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hemolytic-uremic syndrome — screening already-approved drugs against its 4-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHemolytic-uremic syndrome maps to a 4-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 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
complement C5 (C5) — C5 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 eohdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7AD7 · 2.3 Å · ligand ETHANOL (EOH). Experimental structure, not a prediction.
What the evidence adds up to
In a 2009 study of 152 patients with atypical haemolytic-uraemic syndrome, seven unrelated patients carried six different heterozygous missense mutations in the thrombomodulin gene (THBD). That is about 5% of the cohort. In laboratory experiments, normal thrombomodulin bound to complement proteins C3b and factor H and helped inactivate C3b, a step that dampens complement activation. Cultured cells expressing the patient-derived thrombomodulin variants were less able to inactivate C3b and less able to activate procarboxypeptidase B, which normally inactivates the anaphylatoxins C3a and C5a. The mutations therefore impaired the cell’s protection against activated complement.
A 2013 review notes that haemolytic-uraemic syndrome in children can have multiple causes and that the common features — microangiopathic haemolytic anaemia, thrombocytopenia, and renal injury — create diagnostic confusion. The review states that anti-complement therapy was available at that time, making it critical to distinguish the cause quickly so that appropriate acute and long-term treatment can be started. No new trial data or patient outcomes are reported in that review.
A 2016 review describes haemolytic-uraemic syndrome as a thrombotic microvascular disease with microthrombi mainly in the kidney. It lists infection, toxins, anti-endothelial cell antibodies, and drugs as key factors in pathogenesis. The review states that plasma infusion and plasmapheresis have been the most effective treatments and have greatly improved survival. It does not provide specific survival or response rates, nor does it mention any drug by name.
What is still missing is a prospective trial that tests whether screening for thrombomodulin mutations and then targeting complement blockade in those patients improves renal outcomes compared with standard plasma therapy. The 5% prevalence means any such trial would need to recruit a large multicentre cohort to obtain enough mutation-positive patients. No randomised controlled trial has yet been reported for this specific genetic subgroup, and the existing reviews do not stratify outcomes by mutation status.
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.
Multifaceted Hemolytic Uremic Syndrome in Pediatrics
AbstractHemolytic uremic syndromes can have devastating consequences in childhood. The common feature of a microangiopathic hemolytic anemia and thrombocytopenia associated with varying degrees of renal injury often creates diagnostic confusion. The inability to arrive at a definitive diagnosis quickly can lead to a delay in initiating renal-preserving and sometimes life-saving treatment. Currently, both the treatment plan and the prognosis vary substantially according to the presumed diagnosis. The availability of anti-complement therapy makes differentiating the cause of the hemolytic uremic syndrome particularly critical. Therefore, it is imperative that consideration be given to each of the possible syndromes at presentation in order to facilitate correct diagnosis and development of an appropriate treatment strategy for both the acute phase and for the long-term care of the patient.
Dicle Medical Journal / Dicle Tip Dergisi · 2011 · 3 citations · open access
Hemolytic uremic syndrome
AbstractHaemolytic uremic syndrome (HUS) is a severe disease with microangiopathic anemia, thrombocytopenia and leading cause of acute renal failure in children. Several etiological factors causing to HUS have been identified, like infections, genetic mutations, drugs, systemic dis­eases. In this review, we present the new classification of the disease, detailed information about pathogenesis, diagnostic methods and therapeutic approaches.
Progress in diagnosis and treatment of hemolytic uremic syndrome
AbstractHemolytic uremic syndrome (HUS) is a thrombotic microvascular disease, characterized by microvascular hemolytic anemia (red blood cell debris can be found), thrombocytopenia, and renal function damage. Micro thrombus mainly distributed in the kidney. Key factors for the pathogenesis includes infection, toxins, anti-endothelial cell antibodies, and drugs. In recent years, new recognition has been made for the causes and pathogenesis of HUS, and plasma infusion and plasmapheresis have been the most effective methods for treatment of HUS, greatly improving the survival rate of HUS patients.
Key words:
Hemolytic uremic syndrome; Child; Diagnosis; Treatment
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.
