DeCure for Combined oxidative phosphorylation defect type 15
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for combined oxidative phosphorylation defect type 15 — 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 moduleCombined oxidative phosphorylation defect type 15 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 combined oxidative phosphorylation defect type 15 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
thioredoxin 2 (TXN2) — TXN2 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 1W4V · 1.8 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Combined oxidative phosphorylation defect type 15 is a mitochondrial disease. The underlying genetics are complex: over 290 genes have been linked to mitochondrial energy generation disorders, but many patients still lack a molecular diagnosis. The oxidative phosphorylation system itself involves five multiprotein complexes under dual genetic control from both mitochondrial and nuclear DNA, and an estimated 1,000 proteins are needed for proper function. Identifying the specific genetic defect in combined OXPHOS deficiencies is described as not an easy task.
No abstract reports any clinical trial, treatment, or outcome data for combined oxidative phosphorylation defect type 15. The 2004 review notes that most OXPHOS disease diagnoses remain difficult and depend on integrating clinical, neuroradiologic, metabolic, biochemical, and pathological evaluations. The 2010 review states that the ultimate goal is to effectively prevent and cure these disorders, but no therapy is described. The 2017 review says understanding of how defects lead to cellular dysfunction is still incomplete.
No survival rates, response rates, or sample sizes are given for any intervention in this disease. The abstracts contain no drug names, no repurposing attempts, and no efficacy claims. What is missing is any clinical trial data, any patient stratification strategy, and any funding directed specifically at testing a drug for this genotype.
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 Biological Chemistry · 2017 · 264 citations · open access
Mitochondrial energy generation disorders: genes, mechanisms, and clues to pathology
AbstractInherited disorders of oxidative phosphorylation cause the clinically and genetically heterogeneous diseases known as mitochondrial energy generation disorders, or mitochondrial diseases. Over the last three decades, mutations causing these disorders have been identified in almost 290 genes, but many patients still remain without a molecular diagnosis. Moreover, while our knowledge of the genetic causes is continually expanding, our understanding into how these defects lead to cellular dysfunction and organ pathology is still incomplete. Here, we review recent developments in disease gene discovery, functional characterization, and shared pathogenic parameters influencing disease pathology that offer promising avenues toward the development of effective therapies.
BioMed Research International · 2010 · 198 citations · open access
Mitochondrial Translation and Beyond: Processes Implicated in Combined Oxidative Phosphorylation Deficiencies
AbstractMitochondrial disorders are a heterogeneous group of often multisystemic and early fatal diseases, which are amongst the most common inherited human diseases. These disorders are caused by defects in the oxidative phosphorylation (OXPHOS) system, which comprises five multisubunit enzyme complexes encoded by both the nuclear and the mitochondrial genomes. Due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system, identifying the genetic defect that underlies an OXPHOS deficiency is not an easy task, especially in the case of combined OXPHOS defects. In the present communication we give an extensive overview of the proteins and processes (in)directly involved in mitochondrial translation and the biogenesis of the OXPHOS system and their roles in combined OXPHOS deficiencies. This knowledge is important for further research into the genetic causes, with the ultimate goal to effectively prevent and cure these complex and often devastating disorders.
Expert Review of Molecular Diagnostics · 2004 · 44 citations
Genetic defects in the oxidative phosphorylation (OXPHOS) system
AbstractThe oxidative phosphorylation (OXPHOS) system consists of five multiprotein complexes and two mobile electron carriers embedded in the lipid bilayer of the mitochondrial inner membrane. With the exception of complex II and the mobile carriers, the other parts of the OXPHOS system are under dual genetic control. Due to this bigenomic control, the inheritance of OXPHOS system defects is either maternal, in the case of mitochondrial DNA mutations, autosomal or X-linked, in the case of nuclear gene defects. In this review, our current genetic understanding of OXPHOS system enzyme deficiencies will be summarized, and future directions that the field might take to unravel so-far genetically unresolved OXPHOS system enzyme deficiencies will be described, with special emphasis on complex I biogenesis.
AbstractAlthough the mitochondrial (mtDNA) encodes only 13 polypeptide subunits of the oxidative phosphorylation (OXPHOS) enzymes, approximately 1,000 proteins are estimated to be necessary for proper OXPHOS function. Over the past ten years, a wide variety of adult and pediatric OXPHOS diseases were found to be caused by or associated with mtDNA mutations and nuclear DNA mutations. These advances enhanced the ability to definitively diagnose patients, develop management plans, and provide genetic counseling. However, in most individuals, diagnosing OXPHOS diseases is difficult and depends on assessing complex data derived from clinical, neuroradiologic, metabolic, biochemical, and pathologic evaluations. As understanding of nuclear OXPHOS genes grows, a more coherent approach to diagnosis, management, and treatment is likely to emerge. This article reviews major classes of OXPHOS diseases, a diagnostic algorithm, and recent advances in this complex field.
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.
