DeCure for Sulfite oxidase deficiency due to molybdenum cofactor deficiency type A
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for sulfite oxidase deficiency due to molybdenum cofactor deficiency type A — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleSulfite oxidase deficiency due to molybdenum cofactor deficiency type A maps to a 3-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 sulfite oxidase deficiency due to molybdenum cofactor deficiency type a 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
molybdenum cofactor synthesis 2 (MOCS2) — MOCS2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5MPO · 2.43 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Molybdenum cofactor deficiency type A is one of two complementation groups identified in cofactor-deficient patients. Coculture of group A and group B fibroblasts, without cell fusion, produced active sulfite oxidase, indicating that a diffusible precursor from group B cells could repair the defect in group A cells. The precursor was too low in concentration for direct characterisation, but a converting enzyme in group A cells appeared to catalyse an activation reaction analogous to one in an E. coli mutant. Direct replacement of the functional molybdenum cofactor was not feasible because of its extreme lability.
The disease is autosomal recessive and results from a lack of sulfite oxidase activity, with severe neurological symptoms. In a late-onset variant, the index case presented at one year with lethargy, inconsolable crying, and a seizure; by 17 months there was mild motor delay, language regression, and feeding difficulties, followed by progressive deterioration with dystonic posturing and further seizures before the condition plateaued. A sibling had isolated lens dislocation and an identical biochemical profile. MRI in both children was strikingly abnormal. A male infant presenting with convulsions and cerebral dysgenesis at birth was diagnosed using a dipstick test showing elevated urinary sulfite.
Prenatal diagnosis is possible by monitoring sulfite oxidase activity in chorionic villus sampling tissue, or by mutation analysis of MOCS1, MOCS2, GEPH, or SUOX. No treatment is described in these abstracts. What is missing is any therapy that can replace the cofactor or its precursor in patients, a practical way to deliver the diffusible precursor identified in cell culture, and clinical trials that test whether precursor administration alters the course of the disease in humans. Patient stratification by complementation group would be essential for any such trial.
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 Clinical Investigation · 1989 · 64 citations · open access
Molybdenum cofactor biosynthesis in humans. Identification of two complementation groups of cofactor-deficient patients and preliminary characterization of a diffusible molybdopterin precursor.
AbstractMolybdenum cofactor deficiency is a devastating disease with affected patients displaying the symptoms of a combined deficiency of sulfite oxidase and xanthine dehydrogenase. Because of the extreme lability of the isolated, functional molybdenum cofactor, direct cofactor replacement therapy is not feasible, and a search for stable biosynthetic intermediates was undertaken. From studies of cocultured fibroblasts from affected individuals, two complementation groups were identified. Coculture of group A and group B cells, without heterokaryon formation, led to the appearance of active sulfite oxidase. Use of conditioned media indicated that a relatively stable, diffusible precursor produced by group B cells could be used to repair sulfite oxidase in group A recipient cells. Although the extremely low levels of precursor produced by group B cells preclude its direct characterization, studies with a heterologous, in vitro reconstitution system suggest that the precursor that accumulates in group B cells is the same as a molybdopterin precursor identified in the Neurospora crassa molybdopterin mutant nit-1, and that a converting enzyme is present in group A cells which catalyzes an activation reaction analogous to that of a converting enzyme identified in the Escherichia coli molybdopterin mutant ChlA1.
Prenatal diagnosis of molybdenum cofactor deficiency and isolated sulfite oxidase deficiency
AbstractMolybdenum cofactor deficiency and isolated sulfite oxidase deficiency are autosomal recessive inborn errors of metabolism with severe neurological symptoms resulting from a lack of sulfite oxidase activity. The deficiencies can be diagnosed prenatally by monitoring sulfite oxidase activity in chorionic villus sampling (CVS) tissue. In those families in which the specific defects have been identified, diagnosis can be achieved by mutation analysis or linkage studies directed at affected genes. These include MOCS1, MOCS2 or GEPH, in cases of molybdenum cofactor deficiency, or SUOX in patients with isolated sulfite oxidase deficiency.
Developmental Medicine & Child Neurology · 1998 · 44 citations · open access
Molybdenum cofactor deficiency – phenotypic variability in a family with a late‐onset variant
AbstractIn a family with molybdenum cofactor deficiency, the onset in the index case was delayed until 1 year of age, when the patient presented with an episode of lethargy and inconsolable crying culminating in a seizure. By 17 months she showed mild motor delay, regression in language skills, and feeding difficulties. Progressive global deterioration followed, associated with sustained irritability, dystonic posturing, and further seizures, before her condition subsequently plateaued. Low plasma uric acid, raised urinary xanthine and hypoxanthine, and positive urinary sulphite were found, which, coupled with assay of sulphite oxidase activity in cultured fibroblasts, confirmed the diagnosis. A sibling had isolated lens dislocation and an identical biochemical profile. MRI in both children was strikingly abnormal. Molybdenum cofactor deficiency may present as a late-onset variant with considerable phenotypic variability.
AbstractA dipstick test strip (Sulfistix) showing elevated urinary sulfite concentrations (400 mg/l) was used in diagnosis of molybdenum cofactor deficiency (MCD), an inborn errror of metabolism, in a male infant presenting with convulsions and cerebral dysgenesis at birth and followed for 3 years at the Klinik fur Kinder und Jugendmedizin, St Marlenhospital, Vechta, Germany.
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.
