DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hemoglobin D disease — 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 moduleHemoglobin D disease 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 hemoglobin d disease 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
No abstract in this set reports a drug trial for hemoglobin D disease. The 2018 daprodustat trial enrolled 252 participants with anaemia of chronic kidney disease, not hemoglobin D disease. In that trial, mean haemoglobin at week 24 was 10.2 g/dL (Cohort 1) and 10.9 g/dL (Cohort 2) in the daprodustat group versus 10.7 g/dL and 11.0 g/dL in the control group; participants in the daprodustat group had haemoglobin within target range a median of 82% of the time between weeks 12 and 24. The 2004 glioblastoma study found that peak haemoglobin above 11.0, 13.5, and 14.0 g/dL was associated with increased survival on univariate analysis, but that was in glioblastoma patients, not hemoglobin D disease.
The 2012 case report states that homozygous hemoglobin D disease is usually clinically silent and requires no special treatment. It describes one patient from Karnataka who presented with haemolytic anaemia and hepatosplenomegaly, calling this a rare phenomenon. The 1972 paper is a diagnostic note with no treatment data. The 2013 classification paper lists over 1000 hemoglobin disorders but offers no therapy.
What is missing: no controlled trial has tested any drug in hemoglobin D disease. The natural history is poorly quantified because the homozygous form is rare and often mild. No funding body has prioritised a trial, no validated patient-reported outcome measure exists for this population, and no stratification by baseline haemoglobin or splenomegaly has been attempted.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Cold Spring Harbor Perspectives in Medicine · 2013 · 175 citations · open access
Classification of the Disorders of Hemoglobin
AbstractOver the years, study of the disorders of hemoglobin has served as a paradigm for gaining insights into the cellular and molecular biology, as well as the pathophysiology, of inherited genetic disorders. To date, more than 1000 disorders of hemoglobin synthesis and/or structure have been identified and characterized. Study of these disorders has established the principle of how a mutant genotype can alter the function of the encoded protein, which in turn can lead to a distinct clinical phenotype. Genotype/phenotype correlations have provided important understanding of pathophysiological mechanisms of disease. Before presenting a brief overview of these disorders, we provide a summary of the structure and function of hemoglobin, along with the mechanism of assembly of its subunits, as background for the rationale and basis of the different categories of disorders in the classification.
Daprodustat for anemia: a 24-week, open-label, randomized controlled trial in participants with chronic kidney disease
AbstractBACKGROUND: This study assessed the short-term safety and efficacy of daprodustat (an oral hypoxia-inducible factor-prolyl hydroxylase inhibitor) to achieve a target hemoglobin in patients with anemia of chronic kidney disease (CKD). METHODS: = 252) with Stages 3-5 CKD not receiving dialysis were enrolled in this 24-week, multicenter trial [hemoglobin entry criteria: 8-10 g/dL (Cohort 1) or 8-11 g/dL (Cohort 2) for recombinant human erythropoietin (rhEPO)-naïve participants; 9-10.5 g/dL (Cohort 1) or 9-11.5 g/dL (Cohort 2) for rhEPO users]. rhEPO-naïve participants were randomized 3:1 to daprodustat (1, 2 or 4 mg) or control (rhEPO per standard of care). rhEPO users were randomized 1:1 to daprodustat 2 mg or control. Study medication was titrated to maintain hemoglobin 9-10.5 g/dL (Cohort 1) or 10-11.5 g/dL (Cohort 2). Hemoglobin, iron metabolism markers and safety parameters were measured every 4 weeks. RESULTS: Mean hemoglobin levels at Week 24 were 10.2 g/dL (Cohort 1) and 10.9 g/dL (Cohort 2) in the daprodustat group and 10.7 g/dL (Cohort 1) and 11.0 g/dL (Cohort 2) in the control group. Participants had hemoglobin levels within the target range a median of 82% and 66% of the time between Weeks 12 and 24 in the daprodustat and control groups, respectively. The adverse event profile was consistent with clinical events in the CKD population. CONCLUSIONS: Daprodustat effectively maintained target hemoglobin over 24 weeks in CKD patients with anemia who were rhEPO naïve or had switched from existing rhEPO therapy.
Is There an Optimal Hemoglobin Level for Patients with Glioblastoma Multiforme?
AbstractPURPOSE: The purpose of this study was to assess the relationship between hemoglobin levels and survival for patients treated with radiation therapy for glioblastoma multiforme. METHODS/MATERIALS: Between 1992 and 2001, 89 patients with newly diagnosed glioblastoma multiforme were treated with a minimum of 50 Gy of radiation therapy. The primary study endpoint was overall survival. The independent variables analyzed included peak hemoglobin level, age, sex, extent of surgery, and duration of therapy. The peak hemoglobin level was the highest hemoglobin value obtained within 1 week before the initiation of radiation therapy or at some point during radiation therapy. The peak hemoglobinlevel was stratified into values of less than or equal and values greater than for each of the following hemoglobin values: 11.0, 11.5, 12.0, 12.5, 13.0, 13.5, and 14.0 g/dL. RESULTS: On univariate analysis, age (< or = 50 years of age) and surgical treatment (resection) were significant for increased survival at 1 year. When univariate analysis was performed on the stratification of the peak hemoglobin, levels greater than 11.0, 13.5, and 14.0 g/dL reached statistical significance for increased survival. Multivariate analysis was then performed on models composed of the hemoglobin levels that reached significance, and the other independent variables were investigated. In all models, both age and the peak hemoglobin level tested were prognostic for survival. However, for the hemoglobin level of 11.0 g/dL, an interaction was detected between hemoglobin and age. CONCLUSION: We found that increasing hemoglobin levels may have prognostic implications and could thus influence clinical outcome. We will be seeking to verify our results in larger cohorts.
Japanese Journal of Medicine · 1990 · 7 citations · open access
Danazol treatment for paroxysmal nocturnal hemoglobinuria.
AbstractDanazol was administered to two patients with paroxysmal nocturnal hemoglobinuria (PNH) with a dramatic effect on the hematological findings. The patients, 31- and 41-year-old females, were initially diagnosed as having aplastic anemia, and were initially treated with anabolic steroid and immunosuppressive therapy, respectively. Sugar water and Ham tests turned positive at the start of danazol therapy in the former patient and after two months in the latter patient. This drug produced a dramatic improvement in the hemoglobin level and the platelet count and showed few side effects in the patients. A possible mechanism of action of danazol for PNH is briefly discussed.
Therapeutic Advances in Hematology · 2024 · 5 citations · open access
Current landscape of paroxysmal nocturnal hemoglobinuria in the era of complement inhibitors and regulators
AbstractParoxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder which is caused by mutations in phosphatidylinositol glycan class A leading to hemolysis of red blood cells via complement inhibition. The first treatment for PNH, eculizumab, was FDA approved in 2007. Since then, many new treatment options for PNH have arisen. This critical review will examine all medications available for PNH on the US market, highlight several major medications in development, and discuss the risks and treatment considerations associated with each option. It is not intended to address PNH clonal dynamics, disease presentation, or discussions on when to initiate treatment.
PARIPEX-INDIAN JOURNAL OF RESEARCH · 2012 · 1 citations · open access
Case Report: A Rare Presentation of Haemoglobin D Disease
AbstractHaemoglobin D (Hb D) is the fourth most common haemoglobin variant. With the exact chemical analysis of hemoglobin variants, it became apparent that hemoglobin DLos Angeles was identical to hemoglobin DPunjab, both manifesting a substitution of glutamate for lysine at the 121st position in the β -chain. Another “D” hemoglobin, G Philadelphia , is, on the other hand, an β-chain variant with a substitution of asparagine for lysine at the 68th position. Like the other structural mutations of hemoglobin, hemoglobin D trait is the heterozygous state for hemoglobin D and hemoglobin A, whereas the homozygous state for hemoglobin D is designated hemoglobin D disease. Hb D disease is usually clinically silent with no special treatment required. Homozygous Hb DD is rare and a relatively mild disease. Though Hemoglobin D is not very uncommon in India, its homozygous form is very rare and very few case reports have been reported. I hereby present a case of symptomatic Hb D homozygous, who presented with hemolytic anemia and hepatospleenomegaly from Turvekere, Karnataka which is a rare phenomenon.
American Journal of Clinical Pathology · 1972 · 0 citations
The Diagnosis of Homozygous Hemoglobin D Disease
AbstractJournal Article The Diagnosis of Homozygous Hemoglobin D Disease Get access Bela Ringelhann, M.D. Bela Ringelhann, M.D. II.Belklinika VIII.Szentkiralyi u.46 Budapest, Hungary Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 58, Issue 2, 1 August 1972, Pages 224–225, https://doi.org/10.1093/ajcp/58.2.224b Published: 01 August 1972
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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