DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital dyserythropoietic anemia — 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 moduleCongenital dyserythropoietic anemia 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 congenital dyserythropoietic anemia 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
interleukin 1 receptor associated kinase 4 (IRAK4) — IRAK4 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 1s,2s,3r,4rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8DKS · 2.45 Å · ligand (1S,2S,3R,4R)-3-({2-[3-(pyrrolidine-1-carbonyl)anilino]thieno[3,2-d]pyrimidin-4-yl}amino)bicyclo[2.2.1]hept-5-ene-2-carboxamide (SO9). Experimental structure, not a prediction.
What the evidence adds up to
In 42 patients with congenital dyserythropoietic anaemia type II, 22 mutations in the SEC23B gene were found, including seven novel ones. Patients with one missense and one nonsense mutation tended to have more severe clinical presentation, lower reticulocyte count, higher serum ferritin, and in some cases greater transfusion needs than patients with two missense mutations. No patient was homozygous or compound heterozygous for two nonsense mutations, and there was overlap between the two categories. The study attempted to define a genotype-phenotype relationship but did not report survival or response rates.
A single case report describes the ninth known patient with congenital dyserythropoietic anaemia type IV, carrying a novel mutation in the KLF1 gene that had not been reported before. No treatment outcomes or quantitative results are given.
A 30-year follow-up of one patient with type I dyserythropoietic anaemia reports that many modes of drug therapy and splenectomy were not helpful. The family history was non-contributory. No response rates or survival data are provided.
A family with mild anaemia characterised by dyserythropoiesis and prominent ringed sideroblasts is described, with autosomal recessive inheritance, microcytosis, poikilocytosis, mild haemolysis, slightly increased haemoglobin A2, and bone marrow erythroid hyperplasia. This was proposed as a previously unreported variant. No treatment or quantitative outcomes are reported.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Haematologica · 2009 · 62 citations · open access
Molecular analysis of 42 patients with congenital dyserythropoietic anemia type II: new mutations in the SEC23B gene and a search for a genotype-phenotype relationship
AbstractBACKGROUND: The most frequent form of congenital dyserythropoietic anemia is the type II form. Recently it was shown that the vast majority of patients with congenital dyserythropoietic anemia type II carry mutations in the SEC23B gene. Here we established the molecular basis of 42 cases of congenital dyserythropoietic anemia type II and attempted to define a genotype-phenotype relationship. DESIGN AND METHODS: SEC23B gene sequencing analysis was performed to assess the diversity and incidence of each mutation in 42 patients with congenital dyserythropoietic anemia type II (25 described exclusively in this work), from the Italian and the French Registries, and the relationship of these mutations with the clinical presentation. To this purpose, we divided the patients into two groups: (i) patients with two missense mutations and (ii) patients with one nonsense and one missense mutation. RESULTS: We found 22 mutations of uneven frequency, including seven novel mutations. Compound heterozygosity for a missense and a nonsense mutation tended to produce a more severe clinical presentation, a lower reticulocyte count, a higher serum ferritin level, and, in some cases, more pronounced transfusion needs, than homozygosity or compound heterozygosity for two missense mutations. Homozygosity or compound heterozygosity for two nonsense mutations was never found. CONCLUSIONS: This study allowed us to determine the most frequent mutations in patients with congenital dyserythropoietic anemia type II. Correlations between the mutations and various biological parameters suggested that the association of one missense mutation and one nonsense mutation was significantly more deleterious that the association of two missense mutations. However, there was an overlap between the two categories.
Journal of Pediatric Hematology/Oncology · 2020 · 15 citations
A Very Rare Congenital Dyserythropoietic Anemia Variant—Type IV in a Patient With a Novel Mutation in the KLF1 Gene: A Case Report and Review of the Literature
AbstractCongenital dyserythropoietic anemias comprise a group of very rare hereditary disorders characterized by ineffective erythropoiesis and distinct morphologic abnormalities of the erythroblasts in the bone marrow. The wide variety of phenotypes observed in these patients makes the diagnosis difficult; identification of the genetic variants is crucial in differential diagnosis and clinical management. We report the nineth case with congenital dyserythropoietic anemia type IV, with a novel mutation that has not been reported before.
American Journal of Clinical Pathology · 1980 · 15 citations
Type I Dyserythropoietic Anemia: A 30-year Follow-ups
AbstractDyserythropoietic anemias are extremely rare disorders which often are misdiagnosed as megaloblastic anemia, DiGuglielmo's syndrome, refractory sideroblastic anemia, paroxysmal nocturnal hemoglobinuria, or other hemolytic anemias. Dyserythropoietic anemia is now subclassified into four types, designated Types I through IV, depending upon light and ultrastructural morphology, erythrocyte immunology, and the course of the disease. This report details the findings in a case of Type I dyserythropoietic anemia that represented a puzzling case of anemia for over 30 years. Many modes of drug therapy, as well as splenectomy, were not helpful. Interestingly, the family history was non-contributory. A brief review of the literature dealing with dyserythropoietic anemia is included.
Variant congenital dyserythropoietic anaemia with ringed sideroblasts
AbstractA family is described with mild anaemia characterized by marked dyserythropoiesis and by prominent ringed sideroblasts. Inheritance is autosomal recessive. Other features include marked microcytosis, poikilocytosis, mild haemolysis, slightly increased haemoglobin A2, bone marrow erythroid hyperplasia and non-specific structural abnormalities of erythroid precursors on electron microscopy. This appears to be a previously unreported type of hereditary anaemia with both dyserythropoiesis and ringed sideroblasts. We propose the designation 'variant congenital dyserythropoietic anaemia with ringed sideroblasts'.
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.
