DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for 3-methylglutaconic aciduria type 8 — 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 8 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 8 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
HtrA serine peptidase 2 (HTRA2) — HTRA2 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 5M3N · 1.649 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Five patients with a severe early-onset phenotype of 3-methylglutaconic aciduria type 8 presented with hypertrophic cardiomyopathy, cataract, hypotonia or developmental delay, lactic acidosis, and normal 3-methylglutaconyl-CoA hydratase activity. The origin of the 3-methylglutaconic acid in these patients was not from leucine degradation but was unidentified, possibly from mevalonate metabolism. A primary mitochondrial disorder was hypothesised for this novel subtype.
In a separate study of 40 children with developmental language delay and 50 age-matched controls, mildly increased urinary 3-methylglutaconic acid was found in 8 of the language-delay children. The combined excretion of 3-methylglutaconic and 3-methylglutaric acid was increased in 9 patients. No differences in other organic acids were seen, and the children with elevated 3-methylglutaconic acid did not differ from other language-delay children in any measured parameter. The authors noted that mildly elevated levels might be a marker of an undefined metabolic disorder and called for further study in larger groups.
A 1962 paper on orotic aciduria describes a rare metabolic disease with megaloblastic anaemia and large urinary orotic acid, due to decreased erythrocyte activities of orotidylic pyrophosphorylase and orotidylic decarboxylase. This is a different disorder from 3-methylglutaconic aciduria type 8 and does not involve 3-methylglutaconic acid.
No treatment, no drug, and no intervention of any kind is reported in any of these abstracts for 3-methylglutaconic aciduria type 8. What is missing is any clinical trial, any patient stratification beyond the five described cases, and any funding for natural history studies or biomarker development.
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 · 2006 · 34 citations
Hypertrophic cardiomyopathy, cataract, developmental delay, lactic acidosis: A novel subtype of 3‐methylglutaconic aciduria
Abstract3-Methylglutaconic aciduria is the biochemical marker of several inherited metabolic diseases. Four types of 3-methylglutaconic aciduria can be distinguished. In the type I form, accumulation of 3-methylglutaconate is due to deficient activity of 3-methylglutaconyl-CoA hydratase, an enzyme of the leucine degradation pathway. In the other forms, 3-methylglutaconic acid is not derived from leucine but is of unidentified origin, possibly derived from other metabolic pathways, such as mevalonate metabolism. We report five patients, all presenting a severe early-onset phenotype characterized by 3-methylglutaconic aciduria, hypertrophic cardiomyopathy, cataract, hypotonia/developmental delay, lactic acidosis, and normal 3-methylglutaconyl-CoA hydratase activity. This peculiar phenotype, for which a primary mitochondrial disorder is hypothesized, identifies a novel subtype of 3-methylglutaconic aciduria.
Journal of Inherited Metabolic Disease · 1999 · 1 citations
Urinary organic acid screening in children with developmental language delay
AbstractThe prevalence of 3-methylglutaconic aciduria was evaluated among children with developmental language disorders. A urine specimen was obtained from 40 children referred for developmental language delay to the Tel-Aviv Child Development Center during 12/96-6/97 and from 50 age-matched controls. Urine organic acids were analysed by gas chromatography-mass spectrometry. Urinary 3-methylglutaconic acid was quantified. A mildly increased excretion of 3-methylglutaconic acid was found in 8 children with developmental language delay. The combined excretion of 3-methylglutaconic and 3-methylglutaric acid was increased in 9 patients. There were no differences in the excretion of other organic acids. The patients with elevated 3-methylglutaconic acid did not differ from the other patients with developmental language disorders in any of the parameters evaluated. Mildly elevated urinary levels of 3-methylglutaconic acid may be a marker of a still undefined metabolic disorder presenting with developmental language delay. A further study in large groups of children with different developmental disorders is mandatory.
Studies on the Enzymatic Defect of Orotic Aciduria.
Abstracts1 April 1962Studies on the Enzymatic Defect of Orotic Aciduria.L. H. Smith Jr., M.D.L. H. Smith Jr., M.D.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-56-4-678_2 SectionsAboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail ExcerptOrotic aciduria is a rare metabolic disease characterized by megaloblastic anemia, resistant to the usual hematinic agents, and the presence of large amounts of urinary orotic acid, a pyrimidine nucleotide precusor. Studies on the surviving siblings and the parents of the propositus of orotic aciduria have demonstrated decreased erythrocyte activities of orotidylic pyrophosphorylase and orotidylic decarboxylase, enzymes which convert orotic acid into uridylic acid. The pattern of inheritance is consistent with that of an autosomal recessive trait. TwoEntamoeba colimutants and a neurospora crassa mutant with somewhat analogous enzyme defects have been studied as examples of "microbiological orotic aciduria."... This content is PDF only. To continue reading please click on the PDF icon. Author, Article, and Disclosure InformationAffiliations: Boston, Mass. (BS) PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 1 April 1962Volume 56, Issue 4Page: 678-678KeywordsEnzymesMegaloblastic anemiaMetabolic disorders Issue Published: 1 April 1962 PDF DownloadLoading ...
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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