DeCure for Congenital nonspherocytic hemolytic anemia
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for congenital nonspherocytic hemolytic anemia — 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 moduleCongenital nonspherocytic hemolytic anemia 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 congenital nonspherocytic hemolytic 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
glucose-6-phosphate dehydrogenase (G6PD) — G6PD 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 napdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6E08 · 1.9 Å · ligand NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NAP). Experimental structure, not a prediction.
What the evidence adds up to
Congenital nonspherocytic hemolytic anemia is a rare autosomal recessive condition defined by the absence of vital enzymes required for glycolysis, such as homozygous glucose phosphate isomerase and red blood cell nucleotide metabolism, which predisposes red cells to haemolysis. No spherocytosis is seen on peripheral smear and there are no signs of immune-mediated destruction. A 2018 case report describes a previously healthy 21-year-old female patient from India with the condition. Earlier literature from 1967 states that a specific diagnosis must be established for guidance in therapy and family counselling, and that diagnostic methods at that time included determination of deficiencies in the activity of certain enzymes.
The 2023 case report concerns adult hereditary spherocytosis, a related but distinct condition, in a 28-year-old male with jaundice, bile duct stone, and splenomegaly but without anaemia. Gene sequencing revealed a novel heterozygous variant of c.1801C>T (p.Q601X) in exon 14 of the SPTB gene. Splenectomy returned his bilirubin levels to normal. This variant may result in truncation of β-hemoglobin in the erythrocyte membrane, leading to loss of normal function, jaundice, and hemolytic anaemia. The patient’s clinical manifestations were hyperjaundice and an absence of typical haemolysis, which caused diagnostic challenges.
A 2015 review states there is no generic treatment for hemolytic anaemia; appropriate management requires determination of the underlying cause. The 1954 report describes two cases of atypical congenital hemolytic anaemia manifest in early infancy, followed until almost two years of age, in whom no haematological abnormalities were found in the parents, transfused normal cells had a shortened life span, and the Coombs’ test was negative. A 1978 review classifies causes of haemolysis as disorders of the membrane, haemoglobin, or metabolism of the erythrocyte; congenital or familial or acquired; and intrinsic or extrinsic.
What is still missing are prospective trials that stratify patients by specific enzyme deficiencies, funding for genetic and enzymatic screening in suspected cases, and controlled studies of splenectomy or other interventions in confirmed congenital nonspherocytic hemolytic anaemia, as opposed to hereditary spherocytosis.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PubMed · 2015 · 4 citations
[Diagnosis and treatment of hemolytic anemia].
AbstractHemolytic anemia is defined as anemia due to a reduction of the RBC lifespan to less than the normal range of approximately 120 days. Patients with anemia and jaundice are often suspected to have hemolysis. Herein, different causes of hemolysis and the diagnostic algorithm are reviewed. Currently, there is no generic treatment for hemolytic anemia. Appropriate management of a patient with hemolytic anemia requires determination of the underlying cause. Treatments for the different causes of hemolytic anemia are also reviewed.
World Journal of Clinical Cases · 2023 · 4 citations · open access
Clinical manifestations of adult hereditary spherocytosis with novel <i>SPTB</i> gene mutations and hyperjaundice: A case report
AbstractBACKGROUND: The aim of the present study was to enhance understanding of the diagnosis and treatment of atypical hereditary spherocytosis (HS), and to broaden the diagnostic thoughts of physicians for patients with jaundice. CASE SUMMARY: A 28-year-old male presented with jaundice, bile duct stone, and splenomegaly, but without anemia. Other causes of jaundice were excluded, and gene sequencing revealed a novel heterozygous variant of c.1801C>T (p.Q601X) in exon 14 of the SPTB (NM_01355436) gene on chromosome 14 (chr14: 65260580) in the patient's blood; the biological parents and child of the patient did not have similar variants. A splenectomy was performed on the patient and his bilirubin levels returned to normal after surgery. Thus, a novel gene variant causing HS was identified. This variant may result in the truncation of β-hemoglobin in the erythrocyte membrane, leading to loss of normal function, jaundice, and hemolytic anemia. The clinical manifestations of the patient were hyperjaundice and an absence of typical hemolysis during the course of the disease, which caused challenges for diagnosis by the clinicians. CONCLUSION: Following a definitive diagnosis, genetic testing and response to treatment identified a gene variant site for a novel hemolytic anemia.
A Case Report of Congenital Non-spherocytic Hemolytic Anemia in a Patient from India
AbstractCongenital non-spherocytic hemolytic anemia (CNSHA) is a rare autosomal recessive condition that presents as a congenital hemolytic anemia. The absence of vital enzymes required for glycolysis such as homozygous glucose phosphate isomerase (GPI) and red blood cell (RBC) nucleotide metabolism predisposes the RBCs to hemolysis. No spherocytosis is seen on peripheral smear as well as no signs of immune-mediated destruction of RBCs. We present a rare case of a previously healthy 21-year-old female patient with CNSHA from India.
AbstractThe recognition, investigation, diagnosis, and treatment of hemolytic anemia are reviewed on the basis of a classification of the causes of hemolysis according to whether they are disorders of the membrane, hemoglobin, or metabolism of the erythrocyte; congenital or familial or acquired; and intrinsic or extrinsic.
AbstractA specific diagnosis must be established in congenital nonspherocytic hemolytic anemia, for guidance in therapy and family counseling. Diagnostic methods have recently progressed rapidly and include determination of deficiencies in the activity of certain enzymes. Further definitions of enzymatic deficiencies are anticipated.
Atypical Congenital Hemolytic Anemia in Early Infancy
AbstractSummary Two cases of atypical congenital hemolytic anemia manifest in early infancy have been described. The children have been followed up until the age of almost two years. In both cases no hematological abnormalities could be found in the parents. Transfused normal cells had a shortened life span when measured according to the Ashby technique and the Coombs' test was negative.
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.
