DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hemochromatosis type 2B — 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 moduleHemochromatosis type 2B 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 hemochromatosis type 2b 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.
What the evidence adds up to
The 1999 study of a large Italian family with 53 living members identified 15 individuals with abnormal serum ferritin, transferrin saturation above 50 percent, or both. Thirteen of those 15 had elevated body iron confirmed by clinical evaluation and liver biopsy and underwent iron-removal therapy; two children did not receive biopsy or therapy. None of the 15 carried the C282Y mutation in the HFE gene. Five of the 15, and also five healthy relatives, carried the H63D mutation, but none were homozygous for it. Sequencing the entire HFE gene found no other mutations, and microsatellite analysis showed no linkage of the iron-overload phenotype with the short arm of chromosome 6, where HFE sits. The conclusion was that hereditary hemochromatosis can occur in adults without pathogenic mutations in the HFE gene.
A 2002 study compared transferrin saturation and unsaturated iron binding capacity (UIBC) in 110 consecutive subjects referred to a hospital clinic. Among them, 44 carried significant HFE mutations (C282Y/C282Y or C282Y/H63D). For those with biochemical expression, the optimum threshold for transferrin saturation was 43 percent, giving a sensitivity of 0.88 and specificity of 0.95. For UIBC, the optimum threshold was 143 microg/dL (25.6 micromol/L), giving a sensitivity of 0.91 and specificity of 0.95. In patients referred with a family history or clinical suspicion of hemochromatosis, both tests were highly reliable predictors of genotype. In patients referred for abnormal liver enzymes without known family history, a normal transferrin saturation or normal UIBC was highly reliable in excluding hemochromatosis. The authors concluded that UIBC and transferrin saturation have equal reliability.
A 2002 commentary noted that a controlled study had shown very few C282Y homozygotes develop clinical disease, and that the homozygous state is necessary but not sufficient for disease expression. A 2000 paper stated that homozygosity for C282Y is associated with hemochromatosis in a high percentage of patients, and that genetic analysis is useful for diagnosis and screening of asymptomatic relatives. A 2001 review described hereditary hemochromatosis as the most common genetic disorder in the United States, often undetected until severe effects appear.
What is still missing is a clear understanding of the non-HFE genetic or environmental factors that cause iron overload in families like the one studied in 1999. No drug therapy is mentioned in any of these abstracts; the only intervention described is iron-removal therapy (phlebotomy). There is no randomised trial comparing screening strategies or treatments in the non-HFE form of the disease, and no data on long-term outcomes in patients without HFE mutations. Patient stratification by genotype beyond C282Y and H63D is not yet possible, and funding for large-scale family studies or prospective cohorts in non-HFE hemochromatosis remains limited.
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 · 1999 · 274 citations · open access
Hereditary Hemochromatosis in Adults without Pathogenic Mutations in the Hemochromatosis Gene
AbstractBACKGROUND AND METHODS: Hereditary hemochromatosis in adults is usually characterized by mutations in the HFE gene on the short arm of chromosome 6. Most patients have a substitution of tyrosine for cysteine at position 282 (C282Y). We studied a large family from Italy that includes persons who have a hereditary iron-overload condition indistinguishable from hemochromatosis but without apparent pathogenic mutations in the HFE gene. We performed biochemical, histologic, and genetic studies of 53 living members of the family, including microsatellite analysis of chromosome 6 and direct sequencing of the HFE gene. RESULTS: Of the 53 family members, 15 had abnormal serum ferritin levels, values for transferrin saturation that were higher than 50 percent, or both. Thirteen of the 15 had elevated body iron levels, diagnosed on the basis of the clinical evaluation and liver biopsy, and underwent iron-removal therapy. The other two, both children, did not undergo liver biopsy or iron-removal therapy. None of the 15 members had the C282Y mutation of the HFE gene; 5 of the 15 (as well as 5 healthy relatives) had another mutation of this gene, a substitution of aspartate for histidine at position 63, but none were homozygous for it. No other mutations were found after sequencing of the entire HFE gene for all family members. Microsatellite analysis showed no linkage of the hemochromatosis phenotype with the short arm of chromosome 6, the site of the HFE gene. CONCLUSIONS: Hereditary hemochromatosis can occur in adults who do not have pathogenic mutations in the hemochromatosis gene.
The American Journal of Gastroenterology · 2002 · 27 citations
Unsaturated iron binding capacity and transferrin saturation are equally reliable in detection of HFE hemochromatosis
AbstractOBJECTIVE: Unsaturated iron binding capacity (UIBC) has been proposed as an inexpensive alternative to transferrin saturation for detection of hereditary hemochromatosis. The aim of this study was to compare, in a hospital referral clinic, the reliability of transferrin saturation and UIBC for detection of subjects who have inherited HFE (HLA-asociated iron overload) genotypes predisposing to iron overload. METHODS: Serum transferrin saturation, UIBC, and ferritin were tested in 110 consecutive subjects. Optimum thresholds were determined from receiver operating characteristic curves. RESULTS: Of 110 subjects, 44 carried significant HFE mutations (C282Y/C282Y or C282Y/H63D). In genetically predisposed subjects with biochemical expression, the optimum threshold for transferrin saturation was 43%, giving a sensitivity of 0.88 and specificity 0.95. For UIBC, the optimum threshold was 143 microg/dL (25.6 micromol/L), giving a sensitivity of 0.91 and specificity of 0.95. In patients referred with a family history or clinical suspicion of hemochromatosis, transferrin saturation and UIBC were highly reliable predictors of genotype. In patients referred for investigation of abnormal liver enzymes without a known family history of hemochromatosis, a normal transferrin saturation or normal UIBC was highly reliable in excluding hemochromatosis. CONCLUSIONS: Transferrin saturation and UIBC have equal reliability in ability to predict hemochromatosis. UIBC should be considered as an alternative to transferrin saturation in detection of hemochromatosis.
Tumor necrosis factor α promoter polymorphisms and liver abnormalities of homozygotes for the 845G>A (C282Y) hereditary hemochromatosis mutation
AbstractAlthough many opinions have been offered regarding the penetrance of hemochromatosis in homozygotes for the 845G>A (C282Y) HFE mutation, a controlled study has shown that very few of these individuals develop clinical disease.[1][1] Clearly, the homozygous state is a necessary but not sufficient
Detection of C282Y and H63D in the <i>HFE</i> Gene
AbstractThe gene for hemochromatosis was identified in 1996 and two mutations were found. Homozygosity for one of these, C282Y, is associated with hemochromatosis in a high percentage of patients. Genetic analysis of patient DNA is, therefore, a very useful tool to aid and confirm diagnosis and to screen asymptomatic relatives of patients to identify those at risk of developing this common, easily treated disease.
Norme assurde sulla sicurezza delle macchine agricole
AbstractHereditary hemochromatosis, once thought to be rare, is the most common genetic disorder in the United States. Nonetheless, the condition often goes undetected and untreated until its severe effects have become apparent. What clues can lead you to the diagnosis, and how can you spot them in your patients, before significant morbidity has occurred? In this article, Drs McDonnell and Witte discuss the diagnosis and management of this underrecognized problem as well as the various issues involved in screening. An illustrative case of hemochromatosis is also included.
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.
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