DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for aspartylglucosaminuria — 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 moduleAspartylglucosaminuria 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 aspartylglucosaminuria 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
aspartylglucosaminidase (AGA) — AGA 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 aspdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 1APZ · 2.3 Å · ligand ASPARTIC ACID (ASP). Experimental structure, not a prediction.
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 · 1997 · 12 citations · open access
Aspartylglucosaminuria among Palestinian Arabs
AbstractAspartylglucosaminuria (AGU) is a rare disorder of glycoprotein metabolism caused by the deficiency of the lysosomal enzyme aspartylglucosaminidase (AGA). AGU is inherited as an autosomal recessive trait and occurs with a high frequency in Finland because of a founder effect. While very few patients with AGU have been reported from non-Finnish origin, we diagnosed the disorder in 8 patients originating from 3 unrelated families, all Palestinian Arabs from the region of Jerusalem. The clinical diagnosis of AGU is often difficult, in particular early in the course of the disease, and most of the patients are diagnosed after the age of 5 years. However, since these patients excrete early large amounts of aspartylglucosamine in urine, biochemical screening is easy by urine chromatography.
Journal of Inherited Metabolic Disease · 1980 · 11 citations
Variation of urinary excretion of aspartylglucosamine and associated clinical findings in aspartylglucosaminuria
AbstractThe urinary excretion of aspartylglucosamine (AADG), the main accumulating glycoprotein degradation product in aspartylglucosaminuria (AGU), was studied in 40 patients at various stages of the disease. Only slight variation was found when the amount of AADG excreted by ten AGU patients under 10 years of age was compared with AADG excretion of older patients at a clinically advanced stage of the disease. The 24h AADG excretion of the younger patients was 354 mg compared with 441 mg in the group of ten patients over 20 years of age. Clinical symptoms were unrelated to AADG excretion.
Biochemical Journal · 1992 · 8 citations · open access
Purification and structure of human liver aspartylglucosaminidase
AbstractWe have recently diagnosed aspartylglucosaminuria (AGU) in four members of a Canadian family. AGU is a lysosomal storage disease in which asparagine-linked glycopeptides accumulate to particularly high concentrations in liver, spleen and thyroid of affected individuals. A lesser accumulation of these glycopeptides is seen in the kidney and brain, and they are also excreted in the urine. The altered metabolism in AGU results from a deficiency of the enzyme aspartylglucosaminidase (1-aspartamido-beta-N-acetylglucosamine amidohydrolase), which hydrolyses the asparagine to N-acetylglucosamine linkages of glycoproteins and glycopeptides. We have used human liver as a source of material for the purification of aspartylglucosaminidase. The enzyme has been purified to homogeneity by using heat treatment, (NH4)2SO4 fractionation, and chromatography on concanavalin A-Sepharose, DEAE-Sepharose, sulphopropyl-Sephadex, hydroxyapatite, DEAE-cellulose and Sephadex G-100. Enzyme activity was followed by measuring colorimetrically the N-acetylglucosamine released from aspartylglucosamine at 56 degrees C. The purified enzyme protein ran at a 'native' molecular mass of 56 kDa in SDS/12.5%-PAGE gels, and the enzyme activity could be quantitatively recovered at this molecular mass by using gel slices as enzyme source in the assay. After denaturation by boiling in SDS the 56 kDa protein was lost with the corresponding appearance of polypeptides alpha,beta and beta 1, lacking enzyme activity, at 24.6, 18.4 and 17.4 kDa respectively. Treatment of heat-denatured enzyme with N-glycosidase F resulted in the following decreases in molecular mass; 24.6 to 23 kDa and 18.4 and 17.4 to 15.8 kDa. These studies indicate that human liver aspartylglucosaminidase is composed of two non-identical polypeptides, each of which is glycosylated. The N-termini of alpha,beta and beta 1 were directly accessible for sequencing, and the first 21, 26 and 22 amino acids respectively were identified.
American Journal of Neuroradiology · 2019 · 7 citations · open access
Susceptibility-Weighted Imaging Findings in Aspartylglucosaminuria
AbstractBACKGROUND AND PURPOSE: Aspartylglucosaminuria is a rare lysosomal storage disorder that causes slowly progressive, childhood-onset intellectual disability and motor deterioration. Previous studies have shown, for example, hypointensity in the thalami in patients with aspartylglucosaminuria on T2WI, especially in the pulvinar nuclei. Susceptibility-weighted imaging is a neuroimaging technique that uses tissue magnetic susceptibility to generate contrast and is able to visualize iron and other mineral deposits in the brain. SWI findings in aspartylglucosaminuria have not been reported previously. MATERIALS AND METHODS: Twenty-one patients with aspartylglucosaminuria (10 girls; 7.4-15.0 years of age) underwent 3T MR imaging. The protocol included an SWI sequence, and the images were visually evaluated. Thirteen patients (6 girls, 7.4-15.0 years of age) had good-quality SWI. Eight patients had motion artifacts and were excluded from the visual analysis. Thirteen healthy children (8 girls, 7.3-14.1 years of age) were imaged as controls. RESULTS: We found a considerably uniform distribution of decreased signal intensity in SWI in the thalamic nuclei in 13 patients with aspartylglucosaminuria. The most evident hypointensity was found in the pulvinar nuclei. Patchy hypointensities were also found especially in the medial and anterior thalamic nuclei. Moreover, some hypointensity was noted in globi pallidi and substantia nigra in older patients. The filtered-phase images indicated accumulation of paramagnetic compounds in these areas. No abnormal findings were seen in the SWI of the healthy controls. CONCLUSIONS: SWI indicates accumulation of paramagnetic compounds in the thalamic nuclei in patients with aspartylglucosaminuria. The finding may raise the suspicion of this rare disease in clinical practice.
Biochemical Journal · 1976 · 7 citations · open access
Isolation of the liver <i>N</i>-aspartyl-β-glucosaminidase in aspartylglucosaminuria
AbstractThe isolation of liver N-aspartyl-beta-glucosaminidase in human aspartylglucosaminuria, where this enzyme activity is diminished, yields an enzyme molecule with the same molecular weight and pH optimum as the normal enzyme. Its activity is 10% of that of the control preparation. Combination of both enzymes results in the summation of both activities, and the pathological enzyme does not inhibit the control preparation. It is concluded that no change into a totally different isoenzyme has occurred in aspartylglucosaminuria.
e+i Elektrotechnik und Informationstechnik · 1997 · 0 citations
5194 美術館計画における入場者予想と施設計画について : CUSTMERの心理動向把握
AbstractThe isolation of liver N-aspartyl-beta-glucosaminidase in human aspartylglucosaminuria, where this enzyme activity is diminished, yields an enzyme molecule with the same molecular weight and pH optimum as the normal enzyme. Its activity is 10% of that of the control preparation. Combination of both enzymes results in the summation of both activities, and the pathological enzyme does not inhibit the control preparation. It is concluded that no change into a totally different isoenzyme has occurred in aspartylglucosaminuria.
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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