DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for 3-methylglutaconic aciduria type 3 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease module3-methylglutaconic aciduria type 3 maps to a 2-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 3-methylglutaconic aciduria type 3 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.
What the evidence adds up to
Of 977 patients investigated across 50 genetically proven mitochondrial disorders, 11% showed 3-methylglutaconic aciduria. In a separate cohort of 388 patients referred for suspected metabolic disorder, 3% of urine samples contained elevated 3-methylglutaconic acid. The finding was not specific to any single disease pathway; it appeared in organic acidurias, urea cycle disorders, haematological and neuromuscular conditions not previously linked to the metabolite. Among the mitochondrial disorders, 3-methylglutaconic aciduria was more frequent in ATPase-related diseases and in cases with mitochondrial DNA depletion or deletion, but absent in patients with single respiratory chain complex deficiencies. The metabolite was a consistent feature only in patients with mutations in AUH, TAZ, SERAC1, OPA3, DNAJC19 and TMEM70 — conditions now grouped as inborn errors of metabolism with 3-methylglutaconic aciduria as a discriminative feature.
Leucine loading tests in 21 patients with different inborn errors of metabolism who present with 3-methylglutaconic aciduria showed that urinary 3-methylglutaconic acid increased only in those with an AUH defect. In all other subtypes — Barth syndrome, MEGDEL syndrome, Costeff syndrome, DCMA syndrome, TMEM70 defect, and not-otherwise-specified 3-MGA-uria — the origin of the metabolite remains unknown and appears independent of leucine catabolism. The leucine loading test therefore offers a simple clinical method to distinguish primary 3-methylglutaconyl-CoA hydratase deficiency from the secondary forms, but it does not explain the underlying mechanism in those secondary cases.
No therapy directed at 3-methylglutaconic aciduria itself is described in these abstracts. The literature reviewed here is observational and classificatory, not interventional. What remains missing is any prospective trial testing whether lowering 3-methylglutaconic acid levels alters clinical outcomes, any validated biomarker that tracks disease severity across the six subtypes, and any funding for a natural history study that could stratify patients by genotype before a treatment trial is designed.
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 · 2013 · 93 citations · open access
3‐Methylglutaconic aciduria—lessons from 50 genes and 977 patients
AbstractElevated urinary excretion of 3-methylglutaconic acid is considered rare in patients suspected of a metabolic disorder. In 3-methylglutaconyl-CoA hydratase deficiency (mutations in AUH), it derives from leucine degradation. In all other disorders with 3-methylglutaconic aciduria the origin is unknown, yet mitochondrial dysfunction is thought to be the common denominator. We investigate the biochemical, clinical and genetic data of 388 patients referred to our centre under suspicion of a metabolic disorder showing 3-methylglutaconic aciduria in routine metabolic screening. Furthermore, we investigate 591 patients with 50 different, genetically proven, mitochondrial disorders for the presence of 3-methylglutaconic aciduria. Three percent of all urine samples of the patients referred showed 3-methylglutaconic aciduria, often in correlation with disorders not reported earlier in association with 3-methylglutaconic aciduria (e.g. organic acidurias, urea cycle disorders, haematological and neuromuscular disorders). In the patient cohort with genetically proven mitochondrial disorders 11% presented 3-methylglutaconic aciduria. It was more frequently seen in ATPase related disorders, with mitochondrial DNA depletion or deletion, but not in patients with single respiratory chain complex deficiencies. Besides, it was a consistent feature of patients with mutations in TAZ, SERAC1, OPA3, DNAJC19 and TMEM70 accounting for mitochondrial membrane related pathology. 3-methylglutaconic aciduria is found quite frequently in patients suspected of a metabolic disorder, and mitochondrial dysfunction is indeed a common denominator. It is only a discriminative feature of patients with mutations in AUH, TAZ, SERAC1, OPA3, DNAJC19 TMEM70. These conditions should therefore be referred to as inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature.
Distribution of ostracode assemblages along the nearshore and offshore areas of Malabar coast, Kerala (west coast of India)
AbstractCurrently, six inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature are known. The "Primary 3-methylglutaconic aciduria," 3-methylglutaconyl-CoA hydratase deficiency or AUH defect, is a disorder of leucine catabolism. For all other subtypes, also denoted "Secondary 3-methylglutaconic acidurias" (TAZ defect or Barth syndrome, SERAC1 defect or MEGDEL syndrome, OPA3 defect or Costeff syndrome, DNAJC19 defect or DCMA syndrome, TMEM70 defect, "not otherwise specified (NOS) 3-MGA-uria"), the origin of 3-methylglutaconic aciduria remains enigmatic but is hypothesized to be independent from leucine catabolism. Here we show the results of leucine loading test in 21 patients with different inborn errors of metabolism who present with 3-methylglutaconic aciduria. After leucine loading urinary 3-methylglutaconic acid levels increased only in the patients with an AUH defect. This strongly supports the hypothesis that 3-methylglutaconic aciduria is independent from leucine breakdown in other inborn errors of metabolism with 3-methylglutaconic aciduria and also provides a simple test to discriminate between primary and secondary 3-methylglutaconic aciduria in regular patient care.
AbstractThe most common clinical syndromes associated with 3-methyl-glutaconic (MGC) aciduria are reviewed by researchers from various centers; Courtwright and Summers Metabolic Disease Center and Baylor Research Institute, Dallas, TX; Shaare Zedek Medical Center, Jerusalem; Free University of Amsterdam; Loewenstein Hospital, Tel-Aviv Univ, Raanana, Israel; and Kennedy Krieger Institute, Baltimore, MD.
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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