DeCure for Glutathione synthetase deficiency with 5-oxoprolinuria
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for glutathione synthetase deficiency with 5-oxoprolinuria — 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 moduleGlutathione synthetase deficiency with 5-oxoprolinuria 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
approvedGlutathioneApproved drug
Structures already discussed alongside glutathione synthetase deficiency with 5-oxoprolinuria in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
GLUTATHIONE S-TRANSFERASE — Glutathione has a real, experimentally solved structure in complex with this target (PDB 13GS, 1.9 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet gshdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 13GS · 1.9 Å · ligand Glutathione (GSH). Experimental structure, not a prediction.
What the evidence adds up to
In cultured fibroblasts from patients with glutathione synthetase deficiency, adding S-acetylglutathione to the medium raised intracellular glutathione content. The 2004 study that reported this did not measure clinical outcomes, survival, or response rates in patients; it was an in vitro experiment on cells. No human trial of S-acetylglutathione for this disease has been described in these abstracts.
Glutathione synthetase deficiency occurs in fewer than 1 in 100,000 individuals worldwide. The 2021 case report describes a newborn boy with the most severe phenotype, diagnosed by clinical features and elevated urinary 5-oxoproline measured by gas chromatography mass spectrometry. The report does not provide any treatment data or follow-up results for that patient.
The 1989 study measured erythrocyte glutathione synthetase activity in patients with 5-oxoprolinuria, their parents, and controls. Homozygotes had a mean activity of 0.10 pkat/mg hemoglobin (range 0.07–0.12), heterozygotes 3.1 (range 2.8–3.7), and controls 6.1 (range 5.4–6.7). The mutant enzyme’s affinity for glycine, gamma-glutamyl-alpha-aminobutyrate, ATP, and Mg2+ was not defective, and its pH optimum, time curves, and temperature dependence did not differ from normal enzyme. The study confirms autosomal recessive inheritance but offers no therapeutic intervention.
What is still missing: any clinical trial of S-acetylglutathione in patients, any data on whether raising glutathione in fibroblasts translates to clinical benefit, and any patient stratification by severity or genotype. Funding for a controlled trial and a practical formulation for human use remain 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.
Journal of Inherited Metabolic Disease · 2004 · 15 citations
<i>S</i>‐Acetylglutathione normalizes intracellular glutathione content in cultured fibroblasts from patients with glutathione synthetase deficiency
AbstractGlutathione synthetase deficiency is an autosomal recessive inherited metabolic defect in the gamma-glutamyl cycle. Decreased intracellular glutathione levels are one of the characteristic biochemical features. In this study we show that addition of S-acetylglutathione to the medium raised intracellular glutathione content in cultured fibroblasts from patients with glutathione synthetase deficiency. This has implications for the treatment of patients with this inborn error of metabolism.
Gas Chromatography Mass Spectrometry Aided Diagnosis of Glutathione Synthetase Deficiency
AbstractGlutathione synthetase (GSS) deficiency is a rare disorder, occurring with a frequency of less than 1 in 100,000 individuals worldwide. The clinical presentation may vary from mild to severe, and manifestations include hemolytic anemia, hyperbilirubinemia, metabolic acidosis, neurological problems, and sepsis. Herein, we present a case of a newborn boy with the most severe phenotype of GSS deficiency, diagnosed based on clinical features and increased urinary 5-oxoproline levels determined via gas chromatography mass spectrometry (GCMS) testing.
Dialnet (Universidad de la Rioja) · 1989 · 0 citations
La historia de amor, la sexualidad y el matrimonio
AbstractThe primary metabolic defect in 5-oxoprolinuria is a generalized deficiency of glutathione synthetase. The activity of this enzyme was determined in cell-free extracts of erythrocytes from patients with 5-oxoprolinuria, their parents and a sibling as well as from normal control individuals. The following activities (pkat/mg of hemoglobin) for glutathione synthetase were obtained: homozygotes mean 0.10 (range 0.07-0.12), heterozygotes mean 3.1 (range 2.8-3.7) and control individuals mean 6.1 (range 5.4-6.7). These results indicate that 5-oxoprolinuria, i.e. the defective gluthione synthetase gene(s), is transmitted by autosomal recessive inheritance. Studies of the kinetics of the low remaining activity of erythrocyte glutathione synthetase in patients with 5-oxoprolinuria failed to reveal defective affinity for glycine, gamma-glutamyl-alpha-aminobutyrate, ATP and Mg2+ ions. Furthermore, the pH optimum, time curves and temperature dependence for the mutant enzyme activity did not significantly differ from the corresponding parameters observed with normal enzyme.
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.
