DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hemochromatosis type 2 — screening already-approved drugs against its 2-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 2 maps to a 2-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 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
homeostatic iron regulator (HFE) — HFE 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1A6Z · 2.6 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 1999 study of a large Italian family with hereditary iron overload indistinguishable from haemochromatosis found no linkage to the short arm of chromosome 6, the site of the HFE gene, and no pathogenic HFE mutations in any affected member. Among 53 living relatives, 15 had abnormal serum ferritin or transferrin saturation above 50%; 13 of those 15 had elevated body iron confirmed by liver biopsy and underwent iron-removal therapy. None of the 15 carried the C282Y mutation; five had the H63D substitution but none were homozygous. The authors concluded that hereditary haemochromatosis can occur in adults without pathogenic HFE mutations.
A 2005 systematic review for the American College of Physicians found that the prevalence of hereditary haemochromatosis in primary care ranged from 1 in 169 to 1 in 556 patients across three studies. Uncontrolled prospective studies of genetic homozygotes did not consistently show progression to overt disease. A serum ferritin below 1000 microg/L predicted absence of cirrhosis, but six studies showed reduced survival once cirrhosis was present. No blinded comparisons of screening tests against liver biopsy or quantitative phlebotomy were identified, and no randomised controlled trials of phlebotomy existed. The review concluded that the available evidence does not demonstrate that benefits of screening outweigh risks and costs.
A 2002 analysis of four US national datasets reported that the prevalence of elevated transferrin saturation ranged from 1% to 6%. When an elevated transferrin saturation of 55% was combined with an elevated ferritin, prevalence fell to 0.65%. Diagnosed haemochromatosis accounted for only 0.01% to 0.03% of ambulatory visits, hospitalisations, and deaths across three years of data. Even when white men were examined separately, the pattern was the same. The authors stated that diagnosed morbidity or mortality from haemochromatosis is considerably lower than would be expected from screening-detected subclinical cases, and that screening recommendations may need to be revisited.
A 2025 report on juvenile haemochromatosis described a patient with novel compound heterozygous mutations in the hemojuvelin gene. The authors suggested that long-term, strategic phlebotomy might offer a novel therapeutic strategy for severe juvenile haemochromatosis, challenging traditional treatment paradigms. What remains missing are prospective natural-history studies that track untreated subclinical iron overload to clinical endpoints, randomised trials comparing early phlebotomy with watchful waiting, and cost-effectiveness analyses that incorporate the low observed disease burden in general populations. For juvenile haemochromatosis specifically, no controlled data exist to confirm that strategic phlebotomy improves outcomes compared with standard phlebotomy schedules.
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.
Screening Primary Care Patients for Hereditary Hemochromatosis with Transferrin Saturation and Serum Ferritin Level: Systematic Review for the American College of Physicians
AbstractBACKGROUND: Therapeutic phlebotomy for hereditary hemochromatosis is relatively safe and presumably efficacious when offered before cirrhosis develops, so screening primary care patients is of substantial interest. PURPOSE: To conduct a systematic review of the evidence on 1) the prevalence of the disease in primary care, 2) the risk for morbid or fatal complications for untreated patients, 3) the diagnostic usefulness of transferrin saturation and serum ferritin level in identifying early disease, 4) the efficacy of early treatment, and 5) whether the benefits of screening outweigh the risks. DATA SOURCES: MEDLINE search from 1966 through April 2004, complemented by reference review of identified original studies and review articles published in English. STUDY SELECTION: PubMed Clinical Queries filters search of prognosis, diagnosis, etiology, or treatment were used depending on the question. Two authors reviewed all titles and abstracts. DATA EXTRACTION: Two investigators independently reviewed extracted data. DATA SYNTHESIS: The prevalence of hereditary hemochromatosis was 1 in 169 patients to 1 in 556 patients (n = 3 studies). Uncontrolled, prospective studies of genetic homozygous patients did not consistently identify a link to overt hereditary hemochromatosis. A serum ferritin level less than 1000 microg/L was predictive of absence of cirrhosis. Six studies demonstrated reduced survival in patients with cirrhosis. Diagnostic studies varied with respect to case definition. No blinded, independent comparisons of screening tests with the gold standard (biopsy or results of quantitative phlebotomy) or randomized, controlled trials of phlebotomy were identified. Cost-effectiveness analysis was limited by lack of prospective data on the natural history of the disease. LIMITATIONS: Varied case definition and lack of prospective cohort studies or randomized trials. CONCLUSIONS: The available evidence does not demonstrate that benefits outweigh the risks and costs of screening for hemochromatosis.
Archives of Internal Medicine · 2002 · 16 citations
Should We Screen for Hemochromatosis?
AbstractBACKGROUND: Population-based hemochromatosis screening has been suggested with the rationale that identification and treatment of subclinical disease would decrease morbidity and mortality due to hemochromatosis. OBJECTIVE: To examine the prevalence of elevated serum transferrin saturation levels and the burden of illness of hemochromatosis in terms of ambulatory visits, hospitalizations, and death in the United States. PARTICIPANTS AND METHODS: Four nationally representative data sets were used for the analysis of the prevalence of hemochromatosis as well as ambulatory care, hospitalizations, and deaths related to hemochromatosis. Participants included men and nonpregnant women aged 18 years and older in the Third National Health and Nutrition Examination Survey (1988-1994) and the 1996, 1997, and 1998 National Ambulatory Care Survey, National Hospital Discharge Survey, and Underlying Cause-of-Death Mortality Files. The data sets were based on single measurements of serum transferrin saturation levels, serum ferritin levels, and healthcare provider-recorded diagnoses according to the International Classification of Diseases, Ninth Revision, Clinical Modification, code for hemochromatosis. RESULTS: The prevalence of elevated serum transferrin saturation levels ranged from 1% to 6%. When an elevated serum transferrin saturation level of 55% is combined with an elevated serum ferritin level, the prevalence decreases from 1.9% to 0.65%. The proportion of diagnosed hemochromatosis utilization out of total ambulatory visits, hospitalizations, and deaths is stable across the measures and the 3 years of data ranging from 0.01% to 0.03%. When white men were examined separately, the relationships remained the same as those among the general population of adults. CONCLUSIONS: Although a substantial proportion of adults whose condition is not currently diagnosed would be identified in a population-based screening program for subclinical hemochromatosis, diagnosed morbidity or mortality owing to hemochromatosis is considerably lower than would be expected. Recommendations for screening programs may need to be revisited.
American Journal of Clinical Pathology · 1976 · 1 citations
The Inheritance of Hemochromatosis
AbstractJournal Article The Inheritance of Hemochromatosis Get access J. P. Goossens J. P. Goossens Department of Internal Medicine Ziekenhuis Lievensberg Bergen op Zoom The Netherlands Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 66, Issue 1, 1 July 1976, Page 155, https://doi.org/10.1093/ajcp/66.1.155 Published: 01 July 1976
World Journal of Clinical Cases · 2025 · 0 citations · open access
Reference diagnosis and treatment process of juvenile hemochromatosis patients
Abstract, published in a renowned medical journal, is an excellent example of meticulous clinical evaluation, comprehensive laboratory testing, advanced imaging, and genetic analysis. The authors identified novel compound heterozygous mutations in the hemojuvelin gene of a patient diagnosed with juvenile hemochromatosis. They suggested that long-term, strategic phlebotomy might offer a novel therapeutic strategy for severe juvenile hemochromatosis, challenging the traditional treatment paradigms.
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.
