DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for 2-hydroxyglutaric aciduria — 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 module2-hydroxyglutaric aciduria 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 2-hydroxyglutaric aciduria 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
isocitrate dehydrogenase (NADP(+)) 2 (IDH2) — IDH2 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5I96 · 1.55 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
The 2-hydroxyglutaric acidurias are a group of genetic disorders defined by elevated urinary concentrations of D-2-hydroxyglutarate, L-2-hydroxyglutarate, or both. Three types are recognised based on the stereoisomeric composition of the accumulated metabolite: D-2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria. Causative genes include L2HGDH, D2HGDH, IDH2, and SLC25A1. Clinical presentation typically involves neurological impairment at a young age, with developmental delay, epilepsy, and characteristic neuroimaging findings, though manifestations are variable and depend on the specific defect.
A 2017 report of the first diagnosed case of L-2-HGA in the Philippines described a child presenting with seizures and developmental delay. The diagnosis was made using locally available biochemical tests that detected increased levels of L-2-hydroxyglutaric acid in urine and other body fluids. The paper reaffirmed the importance of such tests for diagnosing inborn errors of metabolism but did not report any treatment or outcome data for that patient.
No abstract in this set reports any clinical trial, treatment intervention, or drug repurposing attempt for any form of 2-hydroxyglutaric aciduria. The literature remains confined to case reports and reviews of clinical, genetic, and biochemical characterisation. What is missing is any funded clinical trial, a standardised outcome measure for neurological impairment in these disorders, and a clear patient stratification strategy that might allow testing of candidate therapies.
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 · 2012 · 293 citations · open access
Progress in understanding 2‐hydroxyglutaric acidurias
AbstractThe organic acidurias D: -2-hydroxyglutaric aciduria (D-2-HGA), L-2-hydroxyglutaric aciduria (L-2-HGA), and combined D,L-2-hydroxyglutaric aciduria (D,L-2-HGA) cause neurological impairment at young age. Accumulation of D-2-hydroxyglutarate (D-2-HG) and/or L-2-hydroxyglutarate (L-2-HG) in body fluids are the biochemical hallmarks of these disorders. The current review describes the knowledge gathered on 2-hydroxyglutaric acidurias (2-HGA), since the description of the first patients in 1980. We report on the clinical, genetic, enzymatic and metabolic characterization of D-2-HGA type I, D-2-HGA type II, L-2-HGA and D,L-2-HGA, whereas for D-2-HGA type I and type II novel clinical information is presented which was derived from questionnaires.
L-2-Hydroxyglutaric Aciduria – a Rare Type of Organic Aciduria Presenting as Seizures and Developmental Delay in a Filipino Child
AbstractL-2-hydroxyglutaric aciduria (L-2-HGA) is a rare, autosomal recessive organic aciduria with increased levels of L-2hydroxyglutaric acid in the urine and other body fluids. Clinical presentation includes developmental delay, epilepsy, and typical neuroimaging findings. This is a report of the clinical, neuroimaging, and biochemical findings of the first diagnosed case of L-2-hydroxyglutaric aciduria in the Philippines. This paper likewise reaffirms the importance of locally available biochemical tests in diagnosing inborn error of metabolism.
AbstractA group of genetic disorders characterized by elevated urinary concentrations of 2hydroxyglutaric acid.T hree different types have been identified based on the steroisomeric composition of the elevated alpha-hydroxyglutaric acid metabolites.Additionally, the disease may be categorized by the genetic mutation that is causative.Genes associated with 2-hydroxyglutaric aciduria are L2HGDH, D2HGDH, IDH2, and/or SLC25A1.Generally, there is nervous system involvement, but the clinical manifestations are variable and are dependent on the specific type of defect present.
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.
