DeCure for Combined oxidative phosphorylation deficiency 36
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for combined oxidative phosphorylation deficiency 36 — 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 deficiency 36 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 deficiency 36 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.
What the evidence adds up to
Combined oxidative phosphorylation deficiency 36 belongs to a group of mitochondrial disorders caused by defects in the OXPHOS system, which comprises five multisubunit enzyme complexes encoded by both nuclear and mitochondrial genomes. These disorders are described as heterogeneous, often multisystemic, and early fatal, and are among the most common inherited human diseases. Identifying the genetic defect underlying a combined OXPHOS deficiency is not an easy task due to the multitude of proteins and intricacy of the processes required for a properly functioning OXPHOS system. An extensive overview of the proteins and processes directly or indirectly involved in mitochondrial translation and OXPHOS biogenesis has been published, with the stated goal of further research into genetic causes.
A 1951 study showed that low concentrations of 2:4-dinitrophenol (DNP) reversibly uncouple the phosphorylation associated with the oxidation of glutamate, supporting the hypothesis that DNP prevents the use of energy from respiration and glycolysis by inhibiting the formation of high-energy phosphate bonds. The acceleration of respiration and glycolysis in intact cells by low concentrations of DNP was noted, and it was suggested that the Pasteur effect is a consequence of the greater efficiency of aerobic phosphorylation compared with glycolysis, a view consistent with the inhibition of the Pasteur effect by DNP.
A 2001 study investigated evidence of apoptosis in 33 muscle biopsies from patients with genotypically different mitochondrial diseases, including single and multiple deletions and A3243G/A8344G point mutations of mitochondrial DNA. Using the TUNEL reaction as a marker of nuclear DNA fragmentation, as well as antibodies against pro-apoptotic (Fas) and anti-apoptotic (Bcl-2) factors, no significant expression of either protein was found, nor TUNEL positivity. Ultrastructural studies on skeletal muscle from 18 of the 33 patients, examining both phenotypically normal and ragged red fibers, confirmed a lack of morphologic evidence of apoptosis. The authors concluded that genetically determined defects of oxidative phosphorylation do not induce the apoptotic process and that apoptosis is not involved in the pathogenesis of mitochondrial disorders.
No clinical trial data, no tested treatments, and no patient outcomes specific to combined oxidative phosphorylation deficiency 36 were found in these abstracts. What is missing is any clinical trial design, any patient stratification, and any funding directed specifically at this disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Biochemical Journal · 1951 · 120 citations · open access
The inhibition of oxidative phosphorylation
AbstractLoomis & Lipmann (1948) showed that low concen- trations of 2:4-dinitrophenol (DNP) reversibly un- couple the phosphorylation associated with the oxidation of glutamate. This supported the hypo- thesis that agents such as DNP, which prevent the use of the energy provided by respiration and glycolysis, do so by inhibiting the formation of high- energy phosphate bonds (Lardy & Elvehjem, 1945; McElroy, 1947). The acceleration of respiration and glycolysis of intact cells by low concentrations of DNP (see Meyerhof & Geliazkowa, 1947). Johnson (1941) has suggested that the Pasteur effect is a consequence of the greater efficiency of aerobic phosphorylation compared with that associated with glycolysis, a view which is consistent with the inhibition of the Pasteur effect by DNP (Dodds & Greville, 1934). Lynen (1941) has indeed shown that respiration reduces the amount of orthophosphate available for yeast fermentation.
Lack of apoptosis in mitochondrial encephalomyopathies
AbstractBACKGROUND/OBJECTIVE: Apoptosis, or programmed cell death, is an evolutionary conserved mechanism essential for morphogenesis and tissue homeostasis, but it plays an important role also in pathologic conditions, including neurologic disorders. Its execution pathway is critically regulated at the mitochondrial level. Evidence of apoptosis in muscle specimens was investigated in patients with genetically defined mitochondrial encephalomyopathies. METHODS: Thirty-three muscle biopsies from patients with genotypically different mitochondrial diseases (single and multiple deletions, A3243G/A8344G point mutations of the mitochondrial DNA) were studied. The terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) reaction was used as a marker of nuclear DNA fragmentation, as well as antibodies against pro- (Fas) or anti- (Bcl-2) apoptotic factors. Also, because one hallmark of apoptosis is morphologic, ultrastructural studies were performed on skeletal muscle from 18 of 33 patients, examining both phenotypically normal and ragged red fibers. RESULTS: In all muscle biopsies, no significant expression of either pro (Fas) and inhibiting (Bcl-2) apoptosis-related proteins was found, nor TUNEL positivity. This latter finding is confirmed by lack of morphologic evidence of apoptosis in all the fibers examined at the ultrastructural level. CONCLUSION: The authors' findings suggest that genetically determined defects of oxidative phosphorylation do not induce the apoptotic process and that apoptosis is not involved in the pathogenesis of mitochondrial disorders.
Journal of Pharmacy and Pharmacology · 1959 · 12 citations
Oxidative Phosphorylation
AbstractJournal Article Oxidative Phosphorylation Get access J D Judah J D Judah Department of Morbid Anatomy, University College Hospital Medical School, London Search for other works by this author on: Oxford Academic Google Scholar Journal of Pharmacy and Pharmacology, Volume 11, Issue 1, September 1959, Pages 1–16, https://doi.org/10.1111/j.2042-7158.1959.tb12518.x Published: 12 April 2011
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.
