DeCure for Hepatoencephalopathy due to combined oxidative phosphorylation defect type 1
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 — screening already-approved drugs against its 5-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleHepatoencephalopathy due to combined oxidative phosphorylation defect type 1 maps to a 5-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 hepatoencephalopathy due to combined oxidative phosphorylation defect type 1 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
latexin (LXN) — LXN 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 valdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2BO9 · 1.6 Å · ligand VALINE (VAL). Experimental structure, not a prediction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Free Radical Research · 2002 · 149 citations
Oxidative Stress, Mitochondrial Dysfunction, and Epilepsy
AbstractEpilepsy is a common and heterogeneous neurological disorder arising from biochemical and molecular events that are incompletely understood. To effectively manage epilepsies, it is important to understand the mechanisms underlying both seizure-induced brain damage as well as seizure initiation. Oxidative stress is emerging as a mechanism that may play an important role in the etiology of seizure-induced neuronal death. Conversely, epileptic seizures are a common occurrence in mitochondrial diseases arising from defects in oxidative phosphorylation. This review focuses on the emerging role of oxidative stress and mitochondrial dysfunction both as a consequence and cause of epileptic seizures.
Dysfunctional mitochondrial translation and combined oxidative phosphorylation deficiency in a mouse model of hepatoencephalopathy due to <i>Gfm1</i> mutations
AbstractAbstract Hepatoencephalopathy due to combined oxidative phosphorylation deficiency type 1 (COXPD1) is a recessive mitochondrial translation disorder caused by mutations in GFM1 , a nuclear gene encoding mitochondrial elongation factor G1 (EFG1). Patients with COXPD1 typically present hepatoencephalopathy early after birth with rapid disease progression, and usually die within the first few weeks or years of life. We have generated two different mouse models: a Gfm1 knock‐in (KI) harboring the p.R671C missense mutation, found in at least 10 patients who survived more than 1 year, and a Gfm1 knock‐out (KO) model. Homozygous KO mice ( Gfm1 −/− ) were embryonically lethal, whereas homozygous KI ( Gfm1 R671C / R671C ) mice were viable and showed normal growth. R671C mutation in Gfm1 caused drastic reductions in the mitochondrial EFG1 protein content in different organs. Six‐ to eight‐week‐old Gfm1 R671C / R671C mice showed partial reductions of in organello mitochondrial translation and respiratory complex IV enzyme activity in the liver. Compound heterozygous Gfm1 R671C /− showed a more pronounced decrease of EFG1 protein in liver and brain mitochondria, as compared with Gfm1 R671C / R671C mice. At 8 weeks of age, their mitochondrial translation rates were significantly reduced in both tissues. Additionally, Gfm1 R671C /− mice showed combined oxidative phosphorylation deficiency (reduced complex I and IV enzyme activities in liver and brain), and blue native polyacrylamide gel electrophoresis analysis revealed lower amounts of both affected complexes. We conclude that the compound heterozygous Gfm1 R671C /− mouse presents a clear dysfunctional molecular phenotype, showing impaired mitochondrial translation and combined respiratory chain dysfunction, making it a suitable animal model for the study of COXPD1.
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.
