DeCure for Combined oxidative phosphorylation defect type 17
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for combined oxidative phosphorylation defect type 17 — 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 17 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 17 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
elaC ribonuclease Z 2 (ELAC2) — ELAC2 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 naddrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8CBL · 2.79 Å · ligand NICOTINAMIDE-ADENINE-DINUCLEOTIDE (NAD). Experimental structure, not a prediction.
What the evidence adds up to
Combined oxidative phosphorylation defect type 17 is a mitochondrial disease. Mitochondrial diseases are severe genetic disorders caused by mutations in nuclear or mitochondrial DNA that encode proteins of the oxidative phosphorylation system. The oxidative phosphorylation pathway involves over 100 polypeptides, and its five enzyme complexes are assembled through a highly ordered process. Combined OXPHOS defects, which affect more than one complex, are particularly difficult to trace to a specific genetic cause because of the multitude of proteins and the intricacy of the processes required for a functioning system. The 2009 review notes that identifying the underlying genetic defect in combined OXPHOS deficiencies is not an easy task.
No abstract in this set reports any clinical trial, treatment outcome, or survival data for combined oxidative phosphorylation defect type 17. The 2022 review states that the lack of natural history information, the limits of currently available preclinical models, and the wide range of phenotypic presentations have all hampered the development of effective therapies for mitochondrial diseases generally. It describes gene therapy as a viable precision medicine option based on growing preclinical and clinical trial data, but lists obstacles including vector design, targeted tissue tropism, efficient delivery, transgene expression, and immunotoxicity. The 2001 and 2009 papers provide only background on the genetics and complexity of OXPHOS diseases, with no therapeutic results.
The 2009 review states that further research into genetic causes is needed, with the ultimate goal to effectively prevent and cure these complex disorders. What is still missing for combined oxidative phosphorylation defect type 17 specifically is any published clinical trial data, any identified effective treatment, and even a clear genetic characterisation of the defect in most cases. The field lacks natural history data, validated preclinical models, and the patient stratification needed to design meaningful trials.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pharmaceutics · 2022 · 55 citations · open access
Gene Therapy for Mitochondrial Diseases: Current Status and Future Perspective
AbstractMitochondrial diseases (MDs) are a group of severe genetic disorders caused by mutations in the nuclear or mitochondrial genome encoding proteins involved in the oxidative phosphorylation (OXPHOS) system. MDs have a wide range of symptoms, ranging from organ-specific to multisystemic dysfunctions, with different clinical outcomes. The lack of natural history information, the limits of currently available preclinical models, and the wide range of phenotypic presentations seen in MD patients have all hampered the development of effective therapies. The growing number of pre-clinical and clinical trials over the last decade has shown that gene therapy is a viable precision medicine option for treating MD. However, several obstacles must be overcome, including vector design, targeted tissue tropism and efficient delivery, transgene expression, and immunotoxicity. This manuscript offers a comprehensive overview of the state of the art of gene therapy in MD, addressing the main challenges, the most feasible solutions, and the future perspectives of the field.
An Introduction: Oxidative Phosphorylation Diseases
AbstractOxidative phosphorylation (OXPHOS) is responsible for producing much of the adenosine triphosphate that is required by cells. The OXPHOS pathway incorporates over 100 polypeptides whose genes are located in either the nuclear DNA or the mitochondrial DNA (mtDNA). The expression of these genes and the assembly of the five OXPHOS enzyme complexes (complexes I to V) is a highly ordered and coordinated process. A broad array of human diseases result from mutations in either the nuclear or mtDNA genes or even in the systems that coordinate their interactions. Consequently, OXPHOS diseases can have complex inheritance patterns and a wide spectrum of clinical presentations.
Psychological Science and Education · 2009 · 0 citations
Self-Perception Peculiarities of Adolescents at Risk of Getting into Residential Care
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.
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.
