DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Ogden syndrome — 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 moduleOgden syndrome 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 ogden syndrome 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
N-alpha-acetyltransferase 10, NatA catalytic subunit (NAA10) — NAA10 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 ihpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6C9M · 2.8 Å · ligand INOSITOL HEXAKISPHOSPHATE (IHP). Experimental structure, not a prediction.
What the evidence adds up to
Ogden syndrome is an X-linked disorder caused by mutations in the NAA10 gene, which encodes the catalytic subunit of the NatA N-terminal acetyltransferase. Biochemical analysis of cells from affected males carrying the Ser37Pro mutation showed reduced catalytic capacity of the NatA complex, impaired interaction between Naa10 and its auxiliary subunits Naa15 and Naa50, and decreased acetylation of a subset of NatA and NatE substrates. Fibroblasts from these patients displayed abnormal cell migration and proliferation, possibly linked to a perturbed retinoblastoma pathway. As of 2022, fewer than 10 patients had been diagnosed worldwide. A Polish male infant born at 39 weeks with hypotrophy (2400 g) and facial dysmorphism required mechanical ventilation from the first minute, spent 27 days in a neonatal intensive care unit, and was found to have muscular ventricular septal defects, patent foramen ovale, pectus excavatum, clubfoot, and axial hypotonia. Despite treatment, he died at 10 months from pulmonary infections. A 2025 case from Russia described a boy with long QT syndrome, skeletal and facial abnormalities, and mental deficiency who carried a p.Tyr43Ser mutation in NAA10, also found in his sister and mother. During anaesthesia he suffered cardiac arrest due to severe bradycardia and asystole, leading to implantation of a cardioverter-defibrillator.
Prospective data from a 2024 study using Vineland-3 scores showed decline in cognitive function over time in individuals with Ogden syndrome, with the decline present across all sub-domains. There was no significant difference in adaptive behaviour outcomes between seizure and non-seizure groups. Speech therapy was the most commonly used non-pharmaceutical intervention, followed by occupational and physical therapy; more severely affected individuals received more types of therapy. Early intervention analysis found a significant effect only for speech therapy; all other therapies showed non-significant results. The decline in cognitive function was independent of seizure status and of the therapies being received.
The evidence base remains extremely thin. No drug treatment has been tested in any controlled or even uncontrolled trial for Ogden syndrome. The natural history is still being defined from single-figure patient cohorts. What is missing is any funded preclinical or clinical programme to identify or test candidate therapies, a reliable set of outcome measures beyond the Vineland-3 that might capture meaningful change, and a sufficiently large and well-characterised patient cohort to stratify by genotype, cardiac risk, or seizure burden.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Molecular Genetics · 2014 · 129 citations · open access
Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt-acetylation defects
AbstractThe X-linked lethal Ogden syndrome was the first reported human genetic disorder associated with a mutation in an N-terminal acetyltransferase (NAT) gene. The affected males harbor an Ser37Pro (S37P) mutation in the gene encoding Naa10, the catalytic subunit of NatA, the major human NAT involved in the co-translational acetylation of proteins. Structural models and molecular dynamics simulations of the human NatA and its S37P mutant highlight differences in regions involved in catalysis and at the interface between Naa10 and the auxiliary subunit hNaa15. Biochemical data further demonstrate a reduced catalytic capacity and an impaired interaction between hNaa10 S37P and Naa15 as well as Naa50 (NatE), another interactor of the NatA complex. N-Terminal acetylome analyses revealed a decreased acetylation of a subset of NatA and NatE substrates in Ogden syndrome cells, supporting the genetic findings and our hypothesis regarding reduced Nt-acetylation of a subset of NatA/NatE-type substrates as one etiology for Ogden syndrome. Furthermore, Ogden syndrome fibroblasts display abnormal cell migration and proliferation capacity, possibly linked to a perturbed retinoblastoma pathway. N-Terminal acetylation clearly plays a role in Ogden syndrome, thus revealing the in vivo importance of N-terminal acetylation in human physiology and disease.
Frontiers in Genetics · 2022 · 8 citations · open access
Case report: Rare among ultrarare—Clinical odyssey of a new patient with Ogden syndrome
AbstractIntroduction: The definition of ultra-rare disease in terms of its prevalence varies between the sources, usually amounting to ca. 1 in 1.000.000 births. Nonetheless, there are even less frequent disorders, such as Ogden syndrome, which up to this day was diagnosed in less than 10 patients worldwide. They present typically with a variety of developmental defects, including postnatal growth retardation, psychomotor delay and hypotonia. This disorder is caused by the heterozygous mutations in NAA10 gene, which encodes N-alpha-acetyltransferase 10, involved in protein biosynthesis. Therefore, Ogden syndrome belongs to the broader group of genetic disorders, collectively described as NAA10 -related syndrome. Case report: We present a case of a Polish male infant, born in 39. GW with c-section due to the pathological cardiotocography signal. Hypotrophy (2400 g) and facial dysmorphism were noted in the physical examination. From the first minute, the child required mechanical ventilation - a nasal continuous positive airway pressure. For the first 27 days, the patient was treated in a neonatal intensive care unit, where a series of examinations were conducted. On their basis, the presence of the following defects was determined: muscular ventricular septal defects, patent foramen ovale, pectus excavatum, clubfoot and axial hypotonia. Child was then consequently referred to the genetic clinic for counselling. Results of the tests allowed the diagnosis of Ogden syndrome. In the following months the patient’s condition worsened due to the numerous pulmonary infections. Despite the advanced treatment including the variety of medications, the patient eventually died at the age of 10 months. Conclusion: This case report presents a tenth patient diagnosed with Ogden syndrome reported worldwide. It expands the morphologic and clinical phenotype, emphasizing the possible severity of pneumonological disorders in these patients, which may pose a greater threat to a child’s life than more frequently described cardiovascular dysfunctions associated with this syndrome.
Longitudinal Adaptive Behavioral Outcomes in Ogden Syndrome by Seizure Status and Therapeutic Intervention
AbstractOgden syndrome, also known as NAA10-related neurodevelopmental syndrome, is a rare genetic condition associated with pathogenic variants in the NAA10 N-terminal acetylation family of proteins. The condition was initially described in 2011, and is characterized by a range of neurologic symptoms, including intellectual disability and seizures, as well as developmental delays, psychiatric symptoms, congenital heart abnormalities, hypotonia and others. Previously published articles have described the etiology and phenotype of Ogden syndrome, mostly with retrospective analyses; herein, we report prospective data concerning its progress over time. Additionally, we describe the nature of seizures in this condition in greater detail, as well as investigate how already-available non-pharmaceutical therapies impact individuals with NAA10-related neurodevelopmental syndrome. Using Vineland-3 scores, we show decline in cognitive function over time in individuals with Ogden syndrome. Sub-domain analysis found the decline to be present across all modalities. Additional investigation between seizure and non-seizure groups showed no significant difference in adaptive behavior outcomes. Therapy investigation showed speech therapy to be the most commonly used therapy by individuals with NAA10-related neurodevelopmental syndrome, followed by occupational and physical therapy. with more severely affected individuals receiving more types of therapy than their less-severe counterparts. Early intervention analysis was only significantly effective for speech therapy, with analyses of all other therapies being non-significant. Our study portrays the decline in cognitive function over time of individuals within our cohort, independent of seizure status and therapies being received, and highlights the urgent need for the development of effective treatments for Ogden syndrome.
Russian Journal of Cardiology · 2025 · 0 citations · open access
Ogden syndrome — ultra-rare disease variant with a sudden death risk (first description in Russia): a case report
AbstractIntroduction. The article presents a case of a child with long QT syndrome, skeletal and facial abnormalities, and mental deficiency. This symptom complex was a manifestation of an Ogden syndrome, previously undescribed in Russia X-linked disease associated with a NAA10 gene mutation. Brief description . Molecular genetic testing confirmed a mutation (p.Tyr43Ser) in this gene, which was also found in the child’s sister and mother. During anesthesia, the boy suffered cardiac arrest due to severe bradycardia and asystole, due to which a cardioverter-defibrillator was implanted. Discussion. Ogden syndrome is a disease associated with NAA10 gene mutations, which may remain unrecognized. Severe psychoneurological symptoms can mask the cardiac manifestations of the disease for a long time, including long QT syndrome and arrhythmias, which can manifest as dangerous life-threatening arrhythmias and sudden death.
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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