DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Cockayne syndrome — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCockayne syndrome maps to a 3-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 cockayne 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
ERCC excision repair 8, CSA ubiquitin ligase complex subunit (ERCC8) — ERCC8 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8B3D · 2.6 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 100 Cockayne syndrome patients, 8 cases of acute hepatic failure after metronidazole administration were identified, 3 of which were fatal. The interval from first dose to death was 6 to 11 days, and two of those patients also developed acute neurologic deficit. No patient with Cockayne syndrome who received metronidazole was observed to avoid serious adverse effects. A separate report describes a 2-year-old boy who died of acute liver failure 48 hours after starting metronidazole for gastroenteritis, and a 5-year-old boy who developed jaundice, drowsiness, and lethargy after metronidazole and amoxicillin for a dental infection but recovered with supportive care. The mortality after metronidazole in Cockayne syndrome due to liver failure is described as very high, and the diagnosis is considered an absolute contraindication to the drug.
Transcriptome analysis of CSB-deficient induced pluripotent stem cells from two patients, differentiated into neurospheres and cerebral organoids, showed dysregulated biological processes compared to healthy controls. In CSB-deficient neurospheres, the VEGFA-VEGFR2 signalling pathway, vesicle-mediated transport, and head development were upregulated. In CSB-deficient cerebral organoids, brain development, neuron projection development, and synaptic signalling were downregulated. Upregulation of steroid biosynthesis, particularly the cholesterol biosynthesis branch, was common to both timepoints. These findings suggest that Cockayne syndrome involves not only neurodegeneration but also neurodevelopmental dysregulation.
Cockayne syndrome is an autosomal recessive disorder caused by mutations in CSA or CSB, characterised by small stature, microcephaly, intellectual disability, cachectic dwarfism, photosensitivity, hearing and visual loss, bilateral basal ganglia calcifications, and multi-systemic involvement including cardiac, renal, and endocrine complications. Neurological impairment is universal due to generalised brain atrophy, with impaired or absent speech, spasticity, ataxia, limb contractures, and convulsions in 5–10% of patients. Few patients exceed 20 kg or 115 cm.
What is still missing is any clinical trial of a therapeutic agent for Cockayne syndrome itself. The available evidence is limited to case series and laboratory models. No drug has been tested in a controlled trial for this population, and no biomarker or stratification method has been validated to predict which patients might tolerate any given intervention. Funding for natural history studies and preclinical work exists, but resources for a properly designed trial — with endpoints that capture the neurodevelopmental and metabolic components now identified — remain absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
PEDIATRICS · 2015 · 27 citations
Metronidazole Toxicity in Cockayne Syndrome: A Case Series
AbstractCockayne syndrome (CS) is a rare genetic disorder characterized by small stature, intellectual disability, and accelerated pathologic aging. Through the Cockayne Syndrome Natural History Study, we have identified 8 cases of acute hepatic failure after metronidazole administration (8% of our cohort), 3 of which were fatal. The interval between initial administration and death was 6 to 11 days. Two of these patients also experienced acute neurologic deficit. Both hepatotoxicity and acute neurologic deficit have been reported previously as extremely rare adverse events after metronidazole administration. However, we have not identified any patients with CS who have received metronidazole without serious adverse effects. We recommend that a diagnosis of CS be considered an absolute contraindication to the use of metronidazole.
Cockayne Syndrome Patient iPSC-Derived Brain Organoids and Neurospheres Show Early Transcriptional Dysregulation of Biological Processes Associated with Brain Development and Metabolism
AbstractCockayne syndrome (CS) is a rare hereditary autosomal recessive disorder primarily caused by mutations in Cockayne syndrome protein A (CSA) or B (CSB). While many of the functions of CSB have been at least partially elucidated, little is known about the actual developmental dysregulation in this devasting disorder. Of particular interest is the regulation of cerebral development as the most debilitating symptoms are of neurological nature. We generated neurospheres and cerebral organoids utilizing Cockayne syndrome B protein (CSB)-deficient induced pluripotent stem cells derived from two patients with distinct severity levels of CS and healthy controls. The transcriptome of both developmental timepoints was explored using RNA-Seq and bioinformatic analysis to identify dysregulated biological processes common to both patients with CS in comparison to the control. CSB-deficient neurospheres displayed upregulation of the VEGFA-VEGFR2 signalling pathway, vesicle-mediated transport and head development. CSB-deficient cerebral organoids exhibited downregulation of brain development, neuron projection development and synaptic signalling. We further identified the upregulation of steroid biosynthesis as common to both timepoints, in particular the upregulation of the cholesterol biosynthesis branch. Our results provide insights into the neurodevelopmental dysregulation in patients with CS and strengthen the theory that CS is not only a neurodegenerative but also a neurodevelopmental disorder.
Case Reports in Pediatrics · 2020 · 6 citations · open access
Hepatic Failure following Metronidazole in Children with Cockayne Syndrome
AbstractCockayne syndrome is an uncommon autosomal recessive disease characterized by microcephaly, abnormal growth, and pathologic premature aging. The purpose of this report is to evaluate liver failure in children with Cockayne syndrome following metronidazole administration. The first case was a 2-year-old boy with Cockayne syndrome. He had been treated with metronidazole for gastroenteritis. 48 hours after treatment initiation, he was hospitalized due to jaundice, intractable vomiting, and agitation. Unfortunately, he died of acute liver failure. The second case was a 5-year-old boy with Cockayne syndrome as well, who had been treated with amoxicillin and metronidazole for a dental infection. He developed jaundice, drowsiness, lethargy, and anorexia after treatment. At hospital, the child received supportive treatment, and his general condition gradually improved. The liver enzyme levels decreased. He was finally discharged in good general condition. The mortality after metronidazole consumption in patients with Cockayne syndrome due to liver failure is very high. The awareness of the dangers of using metronidazole in these patients is valuable.
AbstractCockayne syndrome is a rare, worldwide, autosomal recessive condition.1 2 It presents most commonly in childhood as a progressive failure of growth and development. Few patients exceed 20 kg in weight or 115 cm in height. Typically the syndrome produces a thin, dwarfed child with deep set eyes, prominent teeth, and a narrow receding chin. The skin is dry, scaly, highly photosensitive, and seems prematurely aged. Neurological impairment is universal owing to generalised brain atrophy. These children are mentally retarded with impaired or absent speech. Mobility is diminished because of a combination of spasticity, ataxia, and limb contractures. Convulsions occur in 5–10% of patients.
Increasing visual loss is expected because of …
Journal of Bangladesh College of Physicians and Surgeons · 2025 · 0 citations · open access
Cockayne Syndrome: A rare neurodegenerative disorder- A case report
AbstractCockayne Syndrome (CS) is a rare autosomal recessive disorder characterised by multi-systemic involvement, including developmental delay, microcephaly, cachectic dwarfism, hearing and visual impairment, cardiac, renal and endocrine complications due to a defect in the DNA repair mechanism. The striking feature of CS is bilateral basal ganglia calcifications. We are presenting a 9-month-old boy presenting with developmental delay, microcephaly, multiple renal abnormalities and the brain CT scan showing bilateral basal ganglia calcifications. J Bangladesh Coll Phys Surg 2025; 43: 303-305
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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