DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for pyruvate dehydrogenase deficiency — screening already-approved drugs against its 11-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease modulePyruvate dehydrogenase deficiency maps to a 11-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 pyruvate dehydrogenase deficiency 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
dihydrolipoamide dehydrogenase (DLD) — DLD 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 faddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6I4R · 1.439 Å · ligand FLAVIN-ADENINE DINUCLEOTIDE (FAD). Experimental structure, not a prediction.
What the evidence adds up to
A four-nucleotide insertion in the E1α gene was identified in one patient with pyruvate dehydrogenase deficiency in 1991. Immunochemical analysis of two boys with primary lactic acidemia and partial PDH complex deficiency found a defect in dephosphorylation and subsequent activation of the E1 alpha subunit. The clinical picture of PDHc deficiency varies from neonatal death with overwhelming lactic acidosis to a relatively benign course early in life; the three main presentations are congenital lactic acidosis, Leigh syndrome, and episodic ataxia. A 2022 case report of a preschool child with a PDHA1 gene mutation describes epilepsy and movement disorders, and notes that the clinical spectrum ranges from lethal forms in the first year of life with lactic acidosis to chronic neurological manifestations without elevated blood lactate.
Treatment consists of a ketogenic diet and cofactor supplementation with thiamine, but successful therapy is rare. No controlled trial data are reported in these abstracts. No response rates, survival statistics, or sample sizes beyond individual cases are given. The 2022 report emphasises the importance of early diagnosis but provides no evidence that early diagnosis changes outcomes.
What is still missing: any prospective trial of thiamine or ketogenic diet with defined endpoints, any biomarker that predicts which patients might respond, any systematic collection of long-term outcomes, and any funding for a multi-centre registry or randomised study. Patient stratification by mutation type or residual enzyme activity has not been attempted in a formal trial.
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 · 1991 · 17 citations
A four‐nucleotide insertion at the E<sub>1</sub><i>α</i> gene in a patient with pyruvate dehydrogenase deficiency
AbstractJournal of Inherited Metabolic DiseaseVolume 14, Issue 5 p. 793-799 JSSIEM Meeting A four-nucleotide insertion at the E1α gene in a patient with pyruvate dehydrogenase deficiency H. Endo, H. Endo Department of Biochemical Genetics, Tohoku University School of Medicine, Sendai, 980 JapanSearch for more papers by this authorS. Miyabayashi, S. Miyabayashi Department of Pediatrics, Tohoku University School of Medicine, Sendai, 980 JapanSearch for more papers by this authorK. Tada, K. Tada Department of Pediatrics, Tohoku University School of Medicine, Sendai, 980 JapanSearch for more papers by this authorK. Narisawa, K. Narisawa Department of Biochemical Genetics, Tohoku University School of Medicine, Sendai, 980 JapanSearch for more papers by this author H. Endo, H. Endo Department of Biochemical Genetics, Tohoku University School of Medicine, Sendai, 980 JapanSearch for more papers by this authorS. Miyabayashi, S. Miyabayashi Department of Pediatrics, Tohoku University School of Medicine, Sendai, 980 JapanSearch for more papers by this authorK. Tada, K. Tada Department of Pediatrics, Tohoku University School of Medicine, Sendai, 980 JapanSearch for more papers by this authorK. Narisawa, K. Narisawa Department of Biochemical Genetics, Tohoku University School of Medicine, Sendai, 980 JapanSearch for more papers by this author First published: 01 September 1991 https://doi.org/10.1007/BF01799952Citations: 10AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume14, Issue5September 1991Pages 793-799 RelatedInformation
Immunochemical analysis of pyruvate dehydrogenase complex in 2 boys with primary lactic acidemia
AbstractWe examined the pyruvate dehydrogenase (PDH) complex using bio- and immunochemical methods with cultured cells derived from 2 boys with mental retardation, ataxia, and primary lactic acidemia due to partial deficiency in the PDH complex. We found a defect in dephosphorylation and the subsequent activation of the E1 alpha subunit of the enzyme.
Oxford University Press eBooks · 2016 · 0 citations
Pyruvate Dehydrogenase Complex Deficiency
AbstractPyruvate dehydrogenase complex (PDHc) deficiency usually first manifests at a young age and is rarely diagnosed in adulthood. The clinical picture varies from neonatal death with overwhelming lactic acidosis to a relatively benign course early in life. The three main presentations are congenital lactic acidosis, Leigh syndrome, and episodic ataxia. Treatment consists of a ketogenic diet and cofactor supplementation with thiamine. Successful therapy is rare.
S S Korsakov Journal of Neurology and Psychiatry · 2022 · 0 citations
A case of epilepsy, movement disorders associated with a mutation in the PDHA1 gene in a preschool child
AbstractDeficiency of the pyruvate dehydrogenase complex E1-alpha subunit is a rare genetic disease with X-linked dominant inheritance. The clinical spectrum of the disease is extremely wide: from lethal forms in children of the first year of life with lactic acidosis to chronic neurological manifestations with structural changes in the central nervous system without increasing the level of lactate in the blood. The authors report a case of this disease in a preschool child and present the results of laboratory and instrumental studies. The importance of early diagnosis of the disease is emphasized.
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.
