DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hereditary spherocytosis — screening already-approved drugs against its 10-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHereditary spherocytosis maps to a 10-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 hereditary spherocytosis 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 isomerase (GPI) — GPI 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 maedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9FCW · 1.4 Å · ligand MALEIC ACID (MAE). Experimental structure, not a prediction.
What the evidence adds up to
Hereditary spherocytosis is a disorder of the erythrocyte membrane, classically described as a Mendelian dominant genetic condition. A retrospective study of 50 patients from 41 families seen at two Manchester children’s hospitals between 1967 and 1979 found that 19 patients (38%) had no family history of spherocytosis, and in 12 patients (24%) tests on the family showed no evidence of disease. The authors concluded that the name hereditary spherocytosis is inaccurate in many cases and suggested congenital spherocytosis as a more appropriate term.
Mutations in five genes — SPTA1, SPTB, ANK1, SLC4A1, and EPB42 — are known to be associated with hereditary spherocytosis, but the mutations are dispersed and nonspecific in some patients, indicating significant heterogeneity in the molecular deficiency. Mutations in the ankyrin-1 gene (ANK1) account for roughly half of all cases; of these, two thirds are inherited in a dominant pattern and the remainder are sporadic. Two novel ANK1 mutations, c.1800+1G>A and c.1196_1196delC, have been reported, with proposed mechanisms of pathogenicity for each. A novel SPTB gene variant, c.5798+1G>A, was identified in one pedigree and shown by in vitro and in vivo splicing experiments to cause a reading frame shift and premature termination codon, probably underlying the disease in that family.
No drug treatment is discussed in any of these abstracts. The literature describes genetic diagnosis and molecular characterisation but provides no data on therapies, survival, response rates, or clinical outcomes from intervention. What is missing is any clinical trial testing a drug for hereditary spherocytosis, any patient stratification beyond mutation type, and any funding directed toward pharmacological treatment rather than genetic description.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Acta Haematologica · 2018 · 120 citations · open access
Molecular Genetic Mechanisms of Hereditary Spherocytosis: Current Perspectives
AbstractWith the widespread use of genetic diagnostic technologies, many novel mutations have been identified in hereditary spherocytosis (HS)-related genes, including SPTA1, SPTB, ANK1, SLC4A1, and EPB42. However, mutations in HS-related genes are dispersed and nonspecific in the diagnosis of some HS patients, indicating significant heterogeneity in the molecular deficiency of HS. It is necessary to provide the molecular and genetic characteristics of these 5 genes for clinicians to examine HS. Here, we reviewed the recent proposed molecular genetic mechanisms of HS.
Archives of Internal Medicine · 1975 · 26 citations
Herediatary spherocytosis. A review
AbstractStudies of the clinical features of hereditary spherocytosis since 1871 and laboratory investigation of the cellular abnormalities since 1940 have led to the characterization of hereditary spherocytosis as a prime example of a Mendelian dominant, genetically determined disorder of the erythrocyte membrane. This review of hereditary spherocytosis emphasizes the contributions of Dr. Lawrence Young and many others of out present understanding of the disease and discusses current studies of the protein abnormality in the membrane of hereditary spherocytes.
AbstractA retrospective study of 50 patients with hereditary spherocytosis (HS) from 41 families seen between 1967 and 1979 at the Royal Manchester Children's Hospital, and Booth Hall Children's Hospital, Manchester, England is described. Nineteen patients (38%) had no family history of spherocytosis and in 12 patients (24%), tests on the family showed no evidence of disease. Various modes of inheritance are discussed in the light of these results. The traditional name for the condition (hereditary spherocytosis) is considered unsuitable as it is clearly inaccurate in many cases. The name congenital spherocytosis would be more appropriate.
[Hereditary spherocytosis due to a novel c.5798+1G>A variant of the SPTB gene].
AbstractOBJECTIVE: To explore the genetic basis of a pedigree affected with hereditary spherocytosis. METHODS: Peripheral blood samples were collected from 17 members of the pedigree. Genomic DNA of the proband was subjected to next generation sequencing. Candidate variant was validated by co-segregation analysis. pCAS2(c.5798+1G) and pCAS2(c.5798+1A) plasmids were constructed by homologous recombination and transfected into 293T cells. Reverse transcription PCR, TA cloning and Sanger sequencing were used to analyze the effect of candidate variant on splicing. Meanwhile, peripheral blood RNAs were extracted to analyze the effect of candidate variant on splicing in vivo. RESULTS: The proband was found to carry a c.5798+1G>A variant of the SPTB gene. The variant has co-segregated with the phenotype in the pedigree. In vitro and in vivo splicing experiments confirmed that the mutation has significantly affected the splicing, resulting in shift of reading frame and produced a premature termination codon. CONCLUSION: The novel c.5798+1G>A variant of the SPTB gene probably underlies the pathogenesis of hereditary spherocytosis in this pedigree.
Hematology & Transfusion International Journal · 2016 · 0 citations
Two novel mutations in the Ankyrin-1 gene associated with Hereditary Spherocytosis
AbstractMutations in the ankyrin-1 gene (ANK1) underlie half of the cases of Hereditary Spherocytosis (HS), and of these, two thirds are due to mutations inherited in a dominant pattern, while the others are due to sporadic mutations. Here we report two novel ANK1 mutations responsible for HS (c.1800+1G>A and c.1196_1196delC) and propose possible mechanisms of pathogenicity for each mutation described.
Zenodo (CERN European Organization for Nuclear Research) · 2017 · 0 citations · open access
Hereditary Spherocytosis In A 17 Year Girl: A Case Report
Abstract<strong><em>Abstract—</em></strong> <em>Hereditary spherocytosis (HS) is a familial hemolytic disorder with marked heterogeneity of clinical features, ranging from an asymptomatic condition to a fulminate haemolytic anaemia. Although a positive family history of spherocytosis increases the risk for this disorder, it may be sporadic in some cases. Seventeen years old girl presented with mild anaemia, jaundice and moderate splenomegaly. Her haematological parameters supported diagnosis of hereditary spherocytosis. Appropriate treatment was started with an advice to patient to undergo splenectomy as an active part of management of the disorder. Mother and other siblings were normal.</em>
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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