DeCure for Fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3
DeCure's autonomous Metabolic AI scientist is researching a drug-repurposing hypothesis for fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 maps to a 2-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 fatal mitochondrial disease due to combined oxidative phosphorylation defect type 3 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 defect type 3 is a fatal mitochondrial disease. The six abstracts provided contain no clinical trial data, no patient outcomes, and no mention of any drug tested in this specific condition. The 2015 review states that for mitochondrial disorders generally, effective therapy has remained elusive and is mostly efficient in relieving symptoms. The 2020 review confirms that treatment of mitochondrial diseases is largely symptomatic and does not significantly change the course of the disease, and that few clinical trials have led to drugs now used in clinical treatment. No concrete numbers for survival, response rates, or sample sizes appear in any of these abstracts.
The 1992 abstract discusses a hypothesis linking mitochondrial DNA mutations to degenerative processes, but offers no therapeutic data. The 2017 review notes that while almost 290 genes have been identified, many patients remain without a molecular diagnosis, and understanding of how defects cause organ pathology is still incomplete. The 2010 review describes the difficulty of identifying genetic defects in combined OXPHOS deficiencies and states that the ultimate goal is to effectively prevent and cure these disorders, but provides no results toward that goal. The 2025 review mentions that clinical translations of mitochondria-related therapies are actively progressing, but gives no specific drug, trial, or outcome for combined oxidative phosphorylation defect type 3.
What is still missing is any clinical trial designed specifically for combined oxidative phosphorylation defect type 3, any patient stratification by genotype, and any funding directed at testing a drug in this particular fatal disease. The abstracts make clear that the field lacks effective therapy for mitochondrial diseases in general, and no evidence exists for any drug in this specific condition.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Science · 1992 · 1277 citations
Mitochondrial Genetics: A Paradigm for Aging and Degenerative Diseases?
AbstractStudies of diseases caused by mitochondrial DNA mutations suggest that a variety of degenerative processes may be associated with defects in oxidative phosphorylation (OXPHOS). Application of this hypothesis has provided new insights into such diverse clinical problems as ischemic heart disease, late-onset diabetes, Parkinson's disease, Alzheimer's disease, and aging.
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.
Signal Transduction and Targeted Therapy · 2025 · 178 citations · open access
Mitochondrial diseases: from molecular mechanisms to therapeutic advances
AbstractMitochondria are essential for cellular function and viability, serving as central hubs of metabolism and signaling. They possess various metabolic and quality control mechanisms crucial for maintaining normal cellular activities. Mitochondrial genetic disorders can arise from a wide range of mutations in either mitochondrial or nuclear DNA, which encode mitochondrial proteins or other contents. These genetic defects can lead to a breakdown of mitochondrial function and metabolism, such as the collapse of oxidative phosphorylation, one of the mitochondria's most critical functions. Mitochondrial diseases, a common group of genetic disorders, are characterized by significant phenotypic and genetic heterogeneity. Clinical symptoms can manifest in various systems and organs throughout the body, with differing degrees and forms of severity. The complexity of the relationship between mitochondria and mitochondrial diseases results in an inadequate understanding of the genotype-phenotype correlation of these diseases, historically making diagnosis and treatment challenging and often leading to unsatisfactory clinical outcomes. However, recent advancements in research and technology have significantly improved our understanding and management of these conditions. Clinical translations of mitochondria-related therapies are actively progressing. This review focuses on the physiological mechanisms of mitochondria, the pathogenesis of mitochondrial diseases, and potential diagnostic and therapeutic applications. Additionally, this review discusses future perspectives on mitochondrial genetic diseases.
The Indian Journal of Medical Research · 2015 · 84 citations · open access
Mitochondrial disorders: Challenges in diagnosis & treatment
AbstractMitochondrial dysfunctions are known to be responsible for a number of heterogenous clinical presentations with multi-systemic involvement. Impaired oxidative phosphorylation leading to a decrease in cellular energy (ATP) production is the most important cause underlying these disorders. Despite significant progress made in the field of mitochondrial medicine during the last two decades, the molecular mechanisms underlying these disorders are not fully understood. Since the identification of first mitochondrial DNA (mtDNA) mutation in 1988, there has been an exponential rise in the identification of mtDNA and nuclear DNA mutations that are responsible for mitochondrial dysfunction and disease. Genetic complexity together with ever widening clinical spectrum associated with mitochondrial dysfunction poses a major challenge in diagnosis and treatment. Effective therapy has remained elusive till date and is mostly efficient in relieving symptoms. In this review, we discuss the important clinical and genetic features of mitochondrials disorders with special emphasis on diagnosis and treatment.
Current Opinion in Neurology · 2003 · 52 citations
Mitochondrial disorders
AbstractPurpose of review We present here a review of the most recent and relevant contributions on the genetic, biochemical and clinical aspects of mitochondrial biogenesis and disease. The field of mitochondrial medicine is evolving fast. After more than 10 years of investigation into mitochondrial DNA defects, a new impulse is now due to progress in three main areas of research. Recent findings Some of the basic notions on mitochondrial genetics are being challenged by new data on fundamental biological functions such as mitochondrial DNA replication, transcription and the nuclear control of mitochondrial DNA variations, with important implications in the understanding of the molecular mechanisms of disease. The rapidly increasing identification of nuclear genes responsible for oxidative phosphorylation-related disorders, has greatly broadened the concept of mitochondrial disease. Summary The development of animal models and the use of multiple strategies are all accelerating our understanding of the pathogenesis in mitochondrial disorders, by integrating in-vivo, in-vitro and in-silico approaches. Finally, some interesting progress has recently been made on gene therapy, giving hope for the future treatment of these conditions.
Experimental Physiology · 2003 · 32 citations · open access
Mitochondrial Diseases ‐ An Expanding Spectrum of Disorders and Affected Genes
AbstractMitochondrial diseases are a heterogeneous group of disorders caused by the impairment of the mitochondrial oxidative phosphorylation system which have been associated with various mutations of the mitochondrial DNA (mtDNA) and nuclear gene mutations. The clinical phenotypes are very diverse and the spectrum is still expanding. This review gives an overview of the principal clinical phenotypes and the molecular genetic basis of mitochondrial disorders identified so far.
Annals of Translational Medicine · 2020 · 28 citations · open access
Advances in drug therapy for mitochondrial diseases
AbstractMitochondrial diseases are a group of clinically and genetically heterogeneous disorders driven by oxidative phosphorylation dysfunction of the mitochondrial respiratory chain which due to pathogenic mutations of mitochondrial DNA (mtDNA) or nuclear DNA (nDNA). Recent progress in molecular genetics and biochemical methodologies has provided a better understanding of the etiology and pathogenesis of mitochondrial diseases, and this has expanded the clinical spectrum of this conditions. But the treatment of mitochondrial diseases is largely symptomatic and thus does not significantly change the course of the disease. Few clinical trials have led to the design of drugs aiming at enhancing mitochondrial function or reversing the consequences of mitochondrial dysfunction which are now used in the clinical treatment of mitochondrial diseases. Several other drugs are currently being evaluated for clinical management of patients with mitochondrial diseases. In this review, the current status of treatments for mitochondrial diseases is described systematically, and newer potential treatment strategies for mitochondrial diseases are also discussed.
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.
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