DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for beta-thalassemia major — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleBeta-thalassemia major maps to a 5-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 beta-thalassemia major 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 striking improvement in life expectancy for homozygous beta-thalassaemia over the past three decades is mainly due to adequate transfusion regimens and effective iron chelation with nightly subcutaneous desferrioxamine. The first successful cure was achieved in 1981 after bone marrow transplantation. The term beta-thalassaemia major denotes a significant shortage or complete absence of beta globin chains, resulting in severe anaemia requiring lifelong transfusions. A 2017 case report describes a beta thalassaemia intermedia phenotype arising from a rare combination of the c.46delT mutation and HPFH 3, noting that close observation of genotype-phenotype correlation may inform molecular therapy.
A 2025 study compared expression of immune checkpoints LAG-3, CTLA-4, TIM-3 and PD-1 in beta-thalassaemia patients treated with HbF-augmenting drugs (n=140) or regular transfusions (n=33) against healthy controls (n=27). LAG-3 expression was increased in patients regardless of treatment. CTLA-4 was increased in patients on regular transfusions. TIM-3 and PD-1 were higher in patients taking HbF augmentation therapy compared to transfusion patients or controls. Very weak to no correlation was found between serum ferritin and any immune checkpoint. The authors attribute these alterations to thalassaemia itself, repeated blood product exposure, recurrent infections, and immunomodulatory drugs.
The 2025 study notes that HbF-augmenting drugs such as hydroxyurea and thalidomide have shown promising results in resource-limited countries, alleviating anaemia and related symptoms, but acknowledges thalidomide’s known immunomodulatory role. No survival or response rate numbers are given for these drugs. The 1997 review mentions desferrioxamine as effective iron chelation but provides no comparative data on newer agents. No randomised trial comparing HbF-augmenting drugs to standard transfusion or chelation is presented.
What is still missing: prospective trials with defined endpoints for HbF-augmenting drugs in beta-thalassaemia major, stratification by genotype and iron burden, and funding for studies that move beyond checkpoint expression to clinical outcomes such as transfusion reduction or survival. The 2025 study is cross-sectional and does not track whether immune checkpoint changes correlate with infection rates or treatment response.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Heart · 2003 · 87 citations · open access
Left ventricular remodelling, and systolic and diastolic function in young adults with thalassaemia major: a Doppler echocardiographic assessment and correlation with haematological data
AbstractOBJECTIVE: To evaluate left ventricular morphology and function in a large population of patients with beta thalassaemia. DESIGN: Echo Doppler assessment of left ventricular function and correlation of cardiovascular data with haematological data. SETTING: Thalassaemia unit in a tertiary referral centre. PATIENTS: 197 young adults with beta thalassaemia, following an adequate transfusional and chelation treatment regimen, without clinical signs of cardiopulmonary involvement. The control group consisted of 213 healthy subjects. RESULTS: Left ventricular volumes, mass index, and mass/volume ratio were increased. Diastolic and systolic shapes were different, the left ventricle maintaining an ellipsoidal shape. The ejection fraction was reduced, and was < 50% in 33 patients. Stroke volume and cardiac index were increased, and systemic vascular resistance was decreased. Fractional shortening and mean velocity of circumferential shortening were decreased. Meridional end systolic and peak systolic stress were increased, as was circumferential end systolic stress. The contractile state was reduced while the functional preload index did not differ. Left ventricular diastolic function, evaluated from the mitral inflow, showed a slightly prolonged isovolumic relaxation time, increased flow velocity integrals, and an increased E/A ratio. Among the haematological data, only serum ferritin showed a weak negative correlation with left ventricular ejection fraction. The patients with the highest serum ferritin (> 2500 ng/ml) had the lowest ejection fraction. CONCLUSIONS: Patients with beta thalassaemia on an adequate transfusion and chelation treatment regimen show abnormal left ventricular remodelling with increased volumes, mass, and mass/volume ratio. Systolic chamber function and contractile state are reduced, with a slightly increased afterload. These findings seem mainly to be related to the increased cardiac output caused by chronic anaemia. Left ventricular performance is better preserved when chelation treatment is adjusted to maintain the serum ferritin concentration at < 1000 ng/ml.
Current Opinion in Hematology · 1997 · 24 citations
Treatment of β-thalassemia
AbstractThe striking improvement in the life expectancy of patients with homozygous beta-thalassemia observed over the past three decades is mainly due to the institution of adequate transfusion regimens and effective iron chelation therapy with nightly subcutaneous desferrioxamine. The prognosis appears particularly favorable for children with thalassemia born since these methods have become widely available. The first successful "cure" of beta-thalassemia was achieved in 1981 after bone marrow transplantation. Recent advances in transfusion techniques, pharmacology, molecular genetics, transplant immunology, and clinical practice today offer considerable promise in further advancing our knowledge and treatment of this disease.
Evaluation of myocardial iron overload using magnetic resonance imaging.
AbstractThe thalassaemias are some of the most common genetic disorders worldwide and, wherever they occur, they constitute a major problem for patients, health providers and the society. The term β-thalassemia denotes a significant shortage or even complete absence of b globin chains resulting from the decreased or absent function of one (heterozygous carrier) or both β genes (homozygous form when the molecular defects are similar or compound heterozygotes when the molecular defects are different). The latter conditions result in an excess of a-chains which continue to be synthesised normally but cannot remain in solution; instead, they precipitate intracellularly causing premature erythroid cell death (ineffective erythropoiesis in the marrow and severe haemolysis in the peripheral blood). The end result is severe anaemia (thalassaemia major or Cooley's anaemia) and the patients need to be transfused for life.
Synergistic Effect of Simvastatin and Romidepsin on Gamma-globin Gene Induction.
AbstractOBJECTIVE: Hemoglobinopathies such as beta-thalassemia and sickle cell disease (SCD) are inherited disorders that are caused by mutations in beta-globin chain. Gamma-globin gene reactivation can ameliorate clinical manifestations of betathalassemia and SCD. Drugs that induce fetal hemoglobin (HbF) can be promising tools for treatment of beta-thalassemia and SCD patients. Recently, it has been shown that Simvastatin (SIM) and Romidepsin (ROM) induce HbF. SIM is a BCL11a inhibitor and ROM is a HDAC inhibitor and both of these drugs are Food and Drug Administration (FDA)-approved for hypercholesterolemia and cutaneous T-cell lymphoma respectively. Our aim was to evaluate the synergistic effects of these drugs in inducing HbF. MATERIALS AND METHODS: day of erythroid differentiation by real-time polymerase chain reaction (PCR) and immunocytochemistry. RESULTS: Our results showed that combination of SIM and ROM significantly increased Gamma-globin gene expression and inhibit BCL11a and HDAC expression compared to results of using each of them alone. SIM and ROM lead to 3.09- fold increase in HbF production compared to the control group. Also, SIM inhibited BCL11a expression (0.065-fold) and ROM inhibited HDAC1 expression (0.47-fold) as two important inhibitors of HbF production after birth. CONCLUSION: We propose combination therapy of these drugs may be ameliorate clinical manifestation in beta-thalassemia and SCD with at least side effects and reduce the need for blood transfusion.
Clinical Case Reports · 2017 · 3 citations · open access
Thalassemia intermedia phenotype resulting from rare combination of c.46delT [Codon15 (‐T)] mutation of beta globin gene and <scp>HPFH</scp> 3
AbstractThe beta thalassemia intermedia phenotype has several genotypes. Hematological and molecular diagnostic approach and logical and sequential conduct of various investigations are necessary for the diagnosis of these disorders. Close observations of the genotype-phenotype correlation will provide a better insight for the development of molecular therapy.
International Journal of General Medicine · 2024 · 3 citations · open access
Global Trends on β-Thalassemia Research Over 10 Years: A Bibliometric Analysis
AbstractPurpose: Thalassemia, an inherited quantitative globin disorder, is the most prevalent monogenic disease globally. While severe alpha thalassemia results in intrauterine death, β-thalassemia manifests during childhood due to the "second conversion of hemoglobin", garnering increased attention in recent decades. Methods: In this study, a bibliometric analysis was conducted of thalassemia articles published in the Web of Science Core Collection database between 2013 and 2023 to establish a comprehensive overview and to identify emerging trends. A total of 5655 studies published between 2013 and 2023 were systematically retrieved, and annual publications demonstrated a steady increase, maintaining a high level over the past decade. Results: emerged as the leading authority in β-thalassemia research. Analysis of research hotspots revealed that the pathogenesis of β-thalassemia is primarily linked to iron overload, anemia, gene mutations, and ineffective erythropoiesis. Furthermore, recent studies focusing on gene editing therapies present promising avenues for future investigation. Conclusion: These findings grasp the research status of β-thalassemia and shed new light on future research frontiers.
Turkish Journal of Hematology · 2025 · 1 citations · open access
Expression of Immune Checkpoints LAG-3, CTLA-4, TIM-3 and PD-1 in Beta Thalassemia patients Treated using HbF Augmentation Therapy and Regular Transfusions
AbstractIntroduction: Beta-thalassemia is an inherited hemoglobin disorder caused by mutations in HBB gene encoding beta globin chains.Severe anemia secondary to defective globin chains, chronic hemolysis and ineffective erythropoiesis requires transfusion support from early childhood.Recently used treatment options with promising results in resource limited countries includes drugs which augment HbF such as hydroxyurea and thalidomide.Although effective in alleviating anemia and related symptoms, these drugs particularly thalidomide has been known for its immunomodulatory role.Similarly, repeated transfusions with compromised immune system increases the risk of infections and weakened immunity.One of the key regulators of immune systems includes immune checkpoints, cell surface molecules on immune cells.Limited studies are available on immune checkpoints such as LAG-3, CTLA-4, TIM-3 and PD-1 expression in thalassemia and its treatment.Objectives: This study aimed to compare LAG-3, CTLA-4, TIM-3, and PD-1 expression in patients treated using HbF augmenting drugs or transfusions and with iron overload.These findings will provide an insight into the immune regulation in betathalassemia in response to treatment.Methods: In this study, the expression of LAG-3, CTLA-4, TIM-3 and PD-1 was quantified using real time PCR in patients managed on blood transfusions (n=33) or HbF augmenting drugs (n=140) and compared with healthy controls (n=27).Results: Our results show an increased expression of LAG-3 in patients regardless of treatment whereas increased CTLA-4 in patients on regular transfusions.On the other hand, the expressions of TIM-3 and PD-1 were higher in patients taking HbF augmentation therapy compared to patients on blood transfusions or the healthy controls.A very weak to no correlation was found between serum ferritin and immune checkpoints.Conclusions: These findings are suggestive of alterations in immune regulation in betathalassemia which could be attributed to thalassemia itself, repeated exposure to blood products, recurrent infections and the immunomodulatory drugs.
Evaluation of prevalence of drug dependence in beta‐thalassemic patients and its risk factors
AbstractObjective: Beta thalassemia is a hereditary disease of hemoglobin synthesis that causes mild to severe microcytic anemia and hemosiderosis in many organs that in severe cases results in organ failure. Many of the patients need blood transfusions. Drug dependence is a recurrent and chronic problem that has both physiological and behavioral aspects.Methods and materials: A total of 207 β thalassemic patients were randomly assigned out of 810 β thalassemic patients that referred to Shiraz Coolys Center in May–July 2005 in the south of Iran. We studied the prevalence of addiction in these patients and compared this with the normal population. We also evaluated the probable risk factors of drug dependence. There was no other study found worldwide at this time.Results: Of these 207 patients, 19 (9.2%) patients were drug dependent and their most common motivation was acquisition of enjoyment. Among the several risk factors that were studied, sex (male), marital status (single), surgical history and family drug addiction history were found to be statistically significant (0.01<p value <0.05).Discussion: Although the prevalence of addiction in thalassemic patients (9.2%) was nearly the same in the normal population of Fars province (10.2%) and Iran (12.5%), it still has a high prevalence and it should be considered as a psychical‐social problem. As this study was the first one done regarding this topic, we hope that in the future more studies will be conducted to help these patients to have a better lifestyle and improve life expectancy and quality of life.
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.
