DeCure for Cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1
DeCure's autonomous Cardio AI scientist is researching a drug-repurposing hypothesis for cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 — 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 moduleCardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 1 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 cardioencephalomyopathy, fatal infantile, due to cytochrome c oxidase deficiency 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
non-SMC condensin II complex subunit H2 (NCAPH2) — NCAPH2 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 9F5W · 7.5 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Of 301 children with CNS and neuromuscular disease referred between 1984 and 1999, 101 had mitochondrial disease. Seventeen had cardiomyopathy, all hypertrophic non-obstructive. Eight had cytochrome-c oxidase deficiency. Left ventricular posterior wall and septal thickness were increased (z-scores +4.6 and +4.3). Nine patients developed heart failure. Eleven patients with cardiomyopathy died, including all eight with cytochrome-c oxidase deficiency. One patient underwent heart transplantation. Mortality in children with mitochondrial disease was higher in those with cardiomyopathy (71%) than those without (26%) (P<0.001). The prognosis for children with cytochrome-c oxidase deficiency and cardiomyopathy appeared particularly unfavourable.
A female infant with a neonatal rapidly progressive fatal course presented with microcephaly, encephalopathy, persistent lactic acidosis, and hypertrophic cardiomyopathy. Postmortem cardiac muscle showed marked complex IV deficiency, while complex IV activity was only slightly decreased in skeletal muscle. Molecular investigations showed compound heterozygosity for two known pathogenic mutations in the COX15 gene. The findings were compared to three previously reported cases.
A homozygous pathogenic variant (c.361G>C; p.[Gly121Arg]) in SCO2 was identified in two brothers with isolated axonal motor neuropathy. Biochemical studies revealed increased level of the mutant SCO2 protein and dysregulation of COX subunits in leukocytes, as well as decrease of proteins involved in the manifestation of neuropathies. Recessive mutations in SCO2 have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency and in only four cases with axonal neuropathy.
No drug treatment is tested or proposed in any of these abstracts. What is missing is any clinical trial, any attempt at pharmacological intervention, any patient stratification beyond genetic diagnosis, and any funding for therapy development in this uniformly fatal 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.
European Heart Journal · 2003 · 242 citations · open access
Cardiomyopathy in children with mitochondrial disease Clinical course and cardiological findings
AbstractAIMS: To determine the frequency of cardiomyopathy in children with mitochondrial disease and describe their clinical course, prognosis and cardiological manifestations. METHODS AND RESULTS: Of 301 children with CNS and neuromuscular disease referred to our institution in 1984 to 1999, 101 had mitochondrial disease. Seventeen patients had cardiomyopathy, diagnosed by echo-Doppler investigations, all of the hypertrophic, non-obstructive type. The onset of symptomatic mitochondrial disease ranged from birth to 10 years of age. Eight children had cytochrome-c oxidase deficiency, while the remaining nine had various defects. Cardiomyopathy was diagnosed from birth to 27 years. Left ventricular posterior wall and septal thickness were both increased: z-scores +4.6+/-2.6 and +4.3+/-1.6 (mean+/-SD), respectively. The left ventricular diastolic diameter z-score, +1.3+/-3.4, and fractional shortening, 24+/-13%, displayed marked variations. Nine patients developed heart failure. Eleven patients with cardiomyopathy died, including all eight with cytochrome-c oxidase deficiency, and one patient underwent a heart transplantation. Mortality in children with mitochondrial disease was higher in those with cardiomyopathy (71%) than those without (26%) (P<0.001). CONCLUSIONS: In children with mitochondrial disease, cardiomyopathy was common (17%) and was associated with increased mortality. The prognosis for children with cytochrome-c oxidase deficiency and cardiomyopathy appeared to be particularly unfavorable.
American Journal of Medical Genetics Part A · 2011 · 41 citations
Infantile cardioencephalopathy due to a COX15 gene defect: Report and review
AbstractWe describe respiratory chain complex IV deficiency (cytochrome c oxidase deficiency) in a female infant with a neonatal rapidly progressive fatal course characterized by microcephaly, encephalopathy, persistent lactic acidosis, and hypertrophic cardiomyopathy. Postmortem cardiac muscle study showed marked complex IV deficiency. In contrast, complex IV activity was only slightly decreased in the skeletal muscle. Subsequent molecular investigations showed compound heterozygosity for two known pathogenic mutations in the COX15 gene. We compare the findings in our patient to those of the three previously reported cases.
Human Mutation · 2022 · 10 citations · open access
Identification of a novel homozygous <i>synthesis of cytochrome c oxidase 2</i> variant in siblings with early‐onset axonal Charcot‐Marie‐Tooth disease
AbstractThe synthesis of cytochrome c oxidase 2 (SCO2) gene encodes for a mitochondrial located metallochaperone essential for the synthesis of the cytochrome c oxidase (COX) subunit 2. Recessive mutations in SCO2 have been reported in several cases with fatal infantile cardioencephalomyopathy with COX deficiency and in only four cases with axonal neuropathy. Here, we identified a homozygous pathogenic variant (c.361G > C; p.[Gly121Arg]) in SCO2 in two brothers with isolated axonal motor neuropathy. To address pathogenicity of the amino acid substitution, biochemical studies were performed and revealed increased level of the mutant SCO2-protein and dysregulation of COX subunits in leukocytes and moreover unraveled decrease of proteins involved in the manifestation of neuropathies. Hence, our combined data strengthen the concept of SCO2 being causative for a very rare form of axonal neuropathy, expand its molecular genetic spectrum and provide first biochemical insights into the underlying pathophysiology.
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.
