DeCure for Non-spherocytic hemolytic anemia due to hexokinase deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for non-spherocytic hemolytic anemia due to hexokinase deficiency — 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 moduleNon-spherocytic hemolytic anemia due to hexokinase deficiency 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 non-spherocytic hemolytic anemia due to hexokinase deficiency 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
hexokinase 1 (HK1) — HK1 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 g6pdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1CZA · 1.9 Å · ligand 6-O-phosphono-alpha-D-glucopyranose (G6P). Experimental structure, not a prediction.
What the evidence adds up to
A 1983 study of a patient with nonspherocytic hemolytic anaemia found hexokinase activity in red cells at about 25% of normal and in platelets at 20–35% of normal. Lymphocyte total hexokinase activity was normal, but type I hexokinase was decreased to about 50% of normal, compensated by the appearance of type III hexokinase in the cytosol rather than in its normal particulate location. The patient was homozygous for the defect; heterozygous parents and three of five sibs had red cell residual activities of 50–67% of normal with no clinical signs. The variant enzyme showed slightly decreased affinity for MgATP2- and a strongly increased inhibition constant for glucose-1,6-P2, while affinity for glucose, heat stability, and pH optimum were normal. Only one subtype of hexokinase I was detected in red cells, compared to at least three in normal controls.
A 1981 report described a 7-year-old Chinese boy with chronic haemolytic anaemia and erythrocyte hexokinase activity approximately 20% of control values. No alterations in kinetics, stability, pH optimum, or electrophoretic patterns could be demonstrated. Subtle differences between maternal and paternal hexokinase characteristics suggested two separate mutant isozymes, with the proband heterozygous for each. The authors noted broad genetic heterogeneity across previously reported hexokinase deficiency cases.
A 2016 case report described the first paediatric patient with congenital nonspherocytic haemolytic anaemia secondary to hexokinase deficiency who became transfusion independent after a matched sibling haematopoietic stem cell transplant using a reduced intensity conditioning regimen. The patient was a 4-year-old boy. No other patients treated this way were reported in the abstract, and no data on long-term outcomes or complications beyond transfusion independence were provided.
What is still missing: no controlled trials exist for any drug therapy in hexokinase deficiency; the only intervention shown to achieve transfusion independence in a single case is stem cell transplantation, which carries its own risks and requires a suitable donor; no pharmacological agent has been tested to increase residual hexokinase activity or reduce haemolysis; patient stratification by genotype and residual enzyme function remains undefined; funding for natural history studies and any drug development is absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 1983 · 44 citations · open access
Generalized hexokinase deficiency in the blood cells of a patient with nonspherocytic hemolytic anemia
AbstractIn a patient with nonspherocytic hemolytic anemia, a hexokinase deficiency was detected in the red cells (residual activity about 25% of normal) and in blood platelets (20%-35% of normal activity). Although the total hexokinase activity in lymphocytes was normal, the amount of hexokinase type I was decreased to about 50% of normal. However, the deficiency was compensated for by the appearance of type III hexokinase. Compartmentation studies with controlled digitonin-induced cell lysis showed that this type III enzyme was localized in the cytosol, while almost all hexokinase activity in normal lymphocytes is particulate. No abnormal lymphocyte functions could be detected. The patient was homozygous for the defect. The parents and three of five sibs of the patient were apparently heterozygous with residual activities of 50%-67% of normal in their red cells, but did not show any clinical signs of hexokinase deficiency. The variant enzyme had a slightly decreased affinity for MgATP2- and a strongly increased inhibition constant for glucose-1,6-P2. Affinity for glucose, heat stability, and pH optimum were normal. In the electrophoretic pattern of red cell hexokinase, only one subtype of hexokinase I could be detected, while in normal red cells, at least three subtypes are present. In the heterozygous individuals, no enzymatic abnormalities could be detected, except for an aberration in the electropherogram of one sib.
American Journal of Hematology · 1981 · 23 citations
Hexokinase “New Hyde Park”: A low activity erythrocyte isozyme in a chinese kindred
AbstractChronic hemolytic anemia in a 7-year-old Chinese boy was found to be associated with decreased activity of erythrocyte hexokinase (approximately 20% of appropriate control values). Alterations in kinetics, stability, pH optimum, or electrophoretic patterns could not be demonstrated with proband hexokinase, but subtle differences between maternal and paternal hexokinase characteristics suggested that two separate mutant isozymes were involved and that the proband was heterozygous for each. Comparisons with previously reported cases of hexokinase deficiency demonstrate the broad genetic heterogeneity that characterizes this disorder.
Biology of Blood and Marrow Transplantation · 2016 · 0 citations · open access
Stable Mixed Donor Chimerism after Allogeneic Stem Cell Transplantation Using a Reduced Intensity Conditioning Regimen in a 4 Year Old Boy with Congenital Non Spherocytic Hemolytic Anemia Secondary to Hexokinase Deficiency
AbstractHexokinase (HK) deficiency is a very rare inherited disorder of the Embden-Meyerhof glycolytic pathway of the erythrocytes where the predominant clinical presentation is congenital non spherocytic hemolytic anemia (CNSHA). The disease severity is variable from mild hemolysis to severe disease that requires chronic blood transfusions with the associated risk of iron overload and alloimmunization. Here we describe the first reported pediatric patient with CNSHA secondary to HK deficiency who became transfusion independent following a matched sibling hematopoietic stem cell transplantation (HSCT) using a reduced intensity conditioning.
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.
