DeCure for Epilepsy, early-onset, 3, with or without developmental delay
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for epilepsy, early-onset, 3, with or without developmental delay — 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 moduleEpilepsy, early-onset, 3, with or without developmental delay 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 epilepsy, early-onset, 3, with or without developmental delay 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
ATPase H+ transporting V0 subunit c (ATP6V0C) — ATP6V0C 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 methyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6WLW · 3.0 Å · ligand tri(methyl)-[2-[[(2~{R})-2-[(~{Z})-octadec-9-enoyl]oxy-3-[(~{E})-1-oxidanylideneoctadec-9-enoxy]propoxy]-oxidanyl-phosphoryl]oxyethyl]azanium (WSS). Experimental structure, not a prediction.
What the evidence adds up to
In a prospective cohort of 613 children followed for a median of 9.7 years, 13.8% met a stringent definition of intractability (two drugs failed, at least one seizure per month for 18 months) and 23.2% met a two-drug failure definition. Intractability was delayed—appearing three or more years after diagnosis—in 31.3% of those meeting the stringent definition and 27.5% of those meeting the two-drug definition. Delayed intractability was more common in focal epilepsy than in catastrophic epilepsy (46.2% vs 14.3% for the stringent definition). Early remission periods preceded delayed intractability in 65.4% to 74.3% of cases. After becoming intractable, 20.5% of children later entered remission and 13.3% were seizure-free at last contact.
Diagnostic delays are common in early-onset epilepsy. In a community-based cohort of 172 children who developed epilepsy before age three, 41% experienced a delay of at least one month from the second seizure to diagnosis. A delay was associated with an average 7.4-point drop in the Vineland motor score at baseline, which persisted for at least three years, and with lower IQ scores 8–9 years later: full-scale IQ was lower by 14.5 points (p = 0.004) and processing speed by 8.4 points (p = 0.06) after adjustment for parental education and clinical factors. Factors contributing to delay included parents not recognising seizures (47 cases), paediatricians missing or deferring diagnosis (15), neurologists deferring diagnosis (7), and scheduling problems (11).
Among 52 infants with neonatal seizures assessed at one year corrected age using Bayley-III scales, only 32.7% showed no developmental delay on any of the five scales. Significant delay (composite score below 70) on at least one scale occurred in 44.2% of patients. Global developmental delay (scores of 55 or less on all five scales) was found in three patients, each of whom also had cerebral palsy and epilepsy. Developmental delay and epilepsy are frequently associated; the causal relationship may be either that epilepsy causes developmental regression (epileptogenic encephalopathy) or that both are manifestations of an underlying neurological pathology.
What is still missing is prospective data on whether reducing diagnostic delays through systematic screening or earlier specialist referral actually improves developmental outcomes, rather than merely reflecting underlying disease severity. No randomised trial has tested whether earlier treatment alters the trajectory of intractability or developmental delay in this population. Patient stratification by syndrome and underlying aetiology remains crude, and the mechanisms linking seizure burden to cognitive decline are not established. Funding for such trials and for biomarker discovery is lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 2006 · 261 citations
How long does it take for epilepsy to become intractable? A prospective investigation
AbstractOBJECTIVE: To determine prospectively when in the course of epilepsy intractability becomes apparent. METHODS: Data are from a prospective cohort of 613 children followed for a median of 9.7 years. Epilepsy syndromes were grouped: focal, idiopathic, catastrophic, and other. Intractability was defined in two ways: (1) 2 drugs failed, 1 seizure/month, on average, for 18 months (stringent), and (2) failure of 2 drugs. Delayed intractability was defined as 3 or more years after epilepsy diagnosis. RESULTS: Eighty-three children (13.8%) met the stringent and 142 (23.2%) met the two-drug definition. Intractability depended on syndrome (p < 0.0001): 26 (31.3%) children meeting stringent and 39 (27.5%) meeting the 2-drug definition had delayed intractability. Intractability was delayed more often in focal than catastrophic epilepsy (stringent: 46.2 vs 14.3%, p = 0.003; two-drug: 40.3 vs 2.2%, p <or= 0.0001). Early remission periods preceded delayed intractability in 65.4 to 74.3% of cases. After becoming intractable, 20.5% subsequently entered remission and 13.3% were seizure free at last contact. INTERPRETATION: Intractable epilepsy may be delayed, especially in focal epilepsy. It often is preceded by a quiescent period, followed by further remissions. These findings help explain why surgically treatable epilepsies may take 20 years or longer before referral to surgery.
Diagnostic delays in children with early onset epilepsy: Impact, reasons, and opportunities to improve care
AbstractPURPOSE: Delayed diagnosis of early onset epilepsy is a potentially important and avoidable complication in epilepsy care. We examined the frequency of diagnostic delays in young children with newly presenting epilepsy, their developmental impact, and reasons for delays. METHODS: Children who developed epilepsy before their third birthday were identified in a prospective community-based cohort. An interval ≥1 month from second seizure to diagnosis was considered a delay. Testing of development at baseline and for up to 3 years after and of intelligence quotient (IQ) 8-9 years later was performed. Detailed parental baseline interview accounts and medical records were reviewed to identify potential reasons for delays. Factors associated with delays included the parent, child, pediatrician, neurologist, and scheduling. RESULTS: Diagnostic delays occurred in 70 (41%) of 172 children. Delays occurred less often if children had received medical attention for the first seizure (p < 0.0001), previously had neonatal or febrile seizures (p = 0.02), had only convulsions before diagnosis (p = 0.005), or had a college-educated parent (p = 0.01). A ≥1 month diagnostic delay was associated with an average 7.4 point drop (p = 0.02) in the Vineland Scales of Adaptive Behavior motor score. The effect was present at diagnosis, persisted for at least 3 years, and was also apparent in IQ scores 8-9 years later, which were lower in association with a diagnostic delay by 8.4 points (p = 0.06) for processing speed up to 14.5 points (p = 0.004) for full scale IQ, after adjustment for parental education and other epilepsy-related clinical factors. Factors associated with delayed diagnosis included parents not recognizing events as seizures (N = 47), pediatricians missing or deferring diagnosis (N = 15), neurologists deferring diagnosis (N = 7), and scheduling problems (N = 11). SIGNIFICANCE: Diagnostic delays occur in many young children with epilepsy. They are associated with substantial decrements in development and IQ later in childhood. Several factors influence diagnostic delays and may represent opportunities for intervention and improved care.
Epileptic Disorders · 2006 · 5 citations · open access
Developmental delay and epilepsy
AbstractABSTRACT Developmental delay can be associated with epilepsy. Epilepsy might be either the cause of the delay of acquisitions (epileptogenic encephalopathy) or only one additional manifestation, the consequence of the underlying neurological pathology (encephalopathy with epilepsy); it is therefore not the only factor responsible for delay. Within the framework of encephalopathies with epilepsy a rigorous diagnosis is necessary with, in particular a cutaneous examination (neuro‐cutaneous syndromes), a precise clinical examination (anoxo‐ischaemic sequelae of the perinatal period), an EEG, a cerebral magnetic resonance imaging (MRI) as well as the search for associated abnomalities (cardiac, renal…). There are also epileptogenic encephalopathies such as age‐related syndromes: Hemiconvulsions‐Hemiplegia‐Epilepsy syndrome; Rasmussen's syndrome; Dravet's syndrome; myoclono‐astatic epilepsy (Doose). Age at onset and type of seizures, as well as ictal and interictal EEG finding provide valuable hints for a specific diagnosis, while other investigation are usually not contributive. Developmental delay and epilepsy are frequently associated. One of the first steps to diagnosis consists in trying to establish the eventual causal role of the epilepsy. Answering this question may prove to be of primary importance for the choice of a therapeutic strategy and/or further etiological investigations.
S S Korsakov Journal of Neurology and Psychiatry · 2018 · 5 citations
Assessment of neurodevelopment in children of different gestational age with neonatal seizures
AbstractAIM: To assess psychomotor development in infants with neonatal seizures (NS) born with different gestational age, by means of Bayley-III scales of infant and toddler development, in their corrected age of 1 year. MATERIAL AND METHODS: The study included 52 infants, who had NS and were born with different gestational age: 28 weeks or less (n=26) - group I, 29-32 weeks (n=16) - group II, 33-36 weeks (n=3) - group III, 37-41 weeks (n=7) - group IV. The infants' neurodevelopment was evaluated in their corrected age of 1 year by means of N. Bayley scales of infant and toddler development, third edition: Cognitive, Language, Motor, Social-Emotional, and Adaptive Behavior. RESULTS AND CONCLUSION: Only 17 (32,7%) of 52 examined infants did not demonstrate any developmental delay on each of five Bayley-III scales. Significant developmental delay (composite score <70) on at least one scale was revealed in 23 (44,2%) patients, including 12 (46,2%) in group I, 5 (31,3%) in group II, 6 (60%) of 10 in the combined group III-IV. In most cases, neurodevelopmental delays were attributed to only one domain and could be indicated as partial. The conclusion about global developmental retardation (the composite scores 55 or less on all five scales) was done in 3 patients, each of whom had a co-morbidity of cerebral palsy and epilepsy.
Neurology Clinical Practice · 2016 · 3 citations · open access
Electrographic status epilepticus in sleep in an adult with cerebral folate deficiency
AbstractA 27-year-old woman was evaluated for developmental delay and intractable epilepsy. She was born via cesarean section at 42-week gestational age. Developmental delay for gross motor skills, fine motor skills, and language was noted since infancy. She was hypotonic and walked by age 3 years. She began speaking at age 2 years. Her social skills were preserved.
Epileptic Disorders · 2023 · 2 citations · open access
A novel <i>GABRG2</i> variant in Sunflower syndrome: A case report and video EEG monitoring
AbstractOBJECTIVE: Sunflower syndrome is a unique photosensitive epilepsy, characterized by heliotropism and stereotyped seizures associated with handwaving. These handwaving events (HWE) are thought to be an ictal phenomenon, although current data are contrasting. Photosensitive epilepsy occurs in 2%-5% of the epilepsy forms and several pathogenic gene variants have been associated with photosensitive epilepsy. However, the genetic etiology of Sunflower syndrome remains unknown. Antiseizure medications (ASM) efficacious in treating photosensitive epilepsy are valproic acid (VPA) and levetiracetam (LEV) although some forms, such as Sunflower syndrome, can be drug-resistant. METHODS AND RESULTS: Here, we report an 8-year-old boy with an early onset of episodes of HWE that was initially categorized as behavioral problems for which risperidone was started. However, the medical history was suggestive of Sunflower syndrome, and subsequent video EEG showed focal mostly temporal and frontotemporal (right and left) epileptiform activity and confirmed the epileptic nature of the HWE. Thus, VPA was started and initially led to seizure frequency reduction. Molecular analyses showed a pathogenic variant in GABRG2 (c.1287G>A p.(Trp429Ter)), which has been associated with photosensitive and generalized epilepsy. SIGNIFICANCE: Overall, clinicians worldwide should be cautious by interpreting HWE and/or other tic-like movements, since an epileptic origin cannot be ruled out. A prompt and correct diagnosis can be made by performing a video EEG early on in the diagnostic process when epileptic seizures are part of the differential diagnosis. Even though the genetic etiology of Sunflower syndrome remains poorly understood, this constellation supports further genetic testing since the detection of a pathogenic variant can help in making correct decisions regarding ASM management.
Is Epilepsy Intractability Predetermined or Acquired?
AbstractHow Long Does it Take for Epilepsy to Become Intractable? A Prospective Investigation Berg AT, Vickrey BG, Testa FM, Levy SR, Shinnar S, DiMario F, Smith S. Ann Neurol 2006;60:73–79. Objective To determine prospectively when in the course of epilepsy intractability becomes apparent. Methods Data are from a prospective cohort of 613 children followed for a median of 9.7 years. Epilepsy syndromes were grouped as focal, idiopathic, catastrophic, and other. Intractability was defined in two ways: (a) two drugs failed, 1 seizure/month, on average, for 18 months (stringent), and (b) failure of two drugs. Delayed intractability was defined as 3 or more years after epilepsy diagnosis. Results Eighty-three children (13.8%) met the stringent and 142 (23.2%) met the two-drug definition. Intractability depended on syndrome ( p < 0.0001): 26 (31.3%) children meeting stringent and 39 (27.5%) meeting the two-drug definition had delayed intractability. Intractability was delayed more often in focal than catastrophic epilepsy (stringent: 46.2 vs 14.3%, p = 0.003; two-drug: 40.3 vs 2.2%, p = 0.0001). Early remission periods preceded delayed intractability in 65.4–74.3% of cases. After becoming intractable, 20.5% subsequently entered remission and 13.3% were seizure free at last contact. Interpretation Intractable epilepsy may be delayed, especially in focal epilepsy. It often is preceded by a quiescent period, followed by further remissions. These findings help explain why surgically treatable epilepsies may take 20 years or longer before referral to surgery.
S S Korsakov Journal of Neurology and Psychiatry · 2016 · 1 citations · open access
Neurodevelopmental disorders in children with epilepsy
AbstractNeurodevelopmental disorders, including intellectual disability, autistic-spectrum disorders, speech disorders, attention deficit hyperactivity disorder (ADHD), learning disabilities, are more prevalent in children with epilepsy compared with the general population. Marked developmental delay and regression of acquired skills are characteristic of epileptic encephalopathies. Conditions, in which neurodevelopmental disorders are associated with the marked epileptiform EEG activity, while clinical epileptic seizures are absent, represent a serious problem. The authors consider the features of epilepsy with electrical status epilepticus during slow-wave sleep, pseudo-Lennox syndrome, Landau-Kleffner syndrome, children autistic epileptiform regression, autosomal-dominant rolandic epilepsy with verbal dispraxy and a combination of epilepsy and subclinical epileptiform EEG activity with developmental dysphasia and ADHD. In addition to the optimization of basic treatment with antiepileptic drugs (AEDs), nootropic drugs which do not increase epileptiform activity (hopantenic acid), are recommended.
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.
