DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for 3-methylglutaconic aciduria, type VIIB — 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 module3-methylglutaconic aciduria, type VIIB 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 3-methylglutaconic aciduria, type viib 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
ClpB family mitochondrial disaggregase (CLPB) — CLPB 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7XBK · 3.7 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
A 1993 paper describes a method for quantifying 3-methylglutaconic acid in urine, plasma, cerebrospinal fluid and amniotic fluid by isotope-dilution gas chromatography/mass spectrometry, using a synthetic carbon-13 labelled standard. The method was applied to normal controls and patients with different forms of 3-methylglutaconic aciduria, but the abstract gives no numerical results for any group.
A 2008 study reports leucine loading tests in 21 patients with various inborn errors of metabolism that present with 3-methylglutaconic aciduria. After leucine loading, urinary 3-methylglutaconic acid levels increased only in patients with an AUH defect (primary 3-methylglutaconic aciduria). In all other subtypes — including Barth syndrome, MEGDEL syndrome, Costeff syndrome, DCMA syndrome, TMEM70 defect, and not-otherwise-specified cases — the origin of the metabolite remains unknown and appears independent of leucine breakdown. The test is proposed as a way to discriminate primary from secondary forms in routine care.
A 2021 analysis of six children with 3-methylglutaconic aciduria notes significant clinical heterogeneity. The most common genetic variants found were splicing variations, followed by nonsense, missense and frameshift mutations. The abstract states that a leucine-free diet and oral L-carnitine therapy are effective for some patients, and that newborn screening is essential for early diagnosis and improved prognosis. No numerical outcomes — survival, response rates, or sample sizes beyond six — are given.
No drug is mentioned in any of these abstracts. What is missing is any controlled trial of diet or carnitine, any data on which patients respond and which do not, and any stratification by genetic subtype beyond the leucine-loading test. The 2021 claim of effectiveness rests on an unspecified number of patients within a sample of six, with no comparator group.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Quantification of 3-methylglutaconic acid in urine, plasma, and amniotic fluid by isotope-dilution gas chromatography/mass spectrometry
AbstractA method is described for quantification of the trace metabolite, 3-methylglutaconic acid, by isotope-dilution gas chromatography/mass spectrometry using synthetic 3-[2,4,6-13C3]methylglutaconic acid. Results are shown for quantification of 3-methylglutaconic acid in plasma, urine, cerebrospinal fluid and amniotic fluid for both normal controls and patients with different forms of 3-methylglutaconic aciduria. A simple method for the synthesis and purification of 3-[2,4,6-13C3]methylglutaconic acid is also described.
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.
[Analysis of six children with 3-methylglutaconic aciduria].
AbstractThere are significant clinical heterogeneities among individuals with 3-methylglutaconic aciduria. The most common pathogenic variants are splicing variations, followed by nonsense, missense and frameshift mutations. Leucine-free diet and oral L-carnitine therapy are effective for some patients. Newborn screening is essential for early diagnosis and improvement of prognosis.
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.
