DeCure for Developmental and epileptic encephalopathy, 2
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 2 — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDevelopmental and epileptic encephalopathy, 2 maps to a 7-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 developmental and epileptic encephalopathy, 2 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
methyl-CpG binding protein 2 (MECP2) — MECP2 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 unxdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6OGK · 1.65 Å · ligand UNKNOWN ATOM OR ION (UNX). Experimental structure, not a prediction.
What the evidence adds up to
In a 2015 study of twelve patients with SCN2A encephalopathy, seizures began on day one to four in eight patients, week two to six in two, and after one year in two. Nine patients had clusters of brief focal seizures with multiple hourly seizures. Three of twelve had infantile spasms. Seven presented with epilepsy of infancy with migrating focal seizures, two with Ohtahara syndrome. Nine patients improved seizure control with sodium channel blockers, including supratherapeutic or high therapeutic phenytoin levels in five. Eight had severe to profound developmental impairment. Three patients were deceased. The same study reviewed 34 other reported cases and suggested three phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group.
A 2022 review proposed the concept of transporter protein disorders and described nine developmental and epileptic encephalopathies caused by solute carrier transporter dysfunction, covering pathogenesis, clinical manifestations, and precise treatment. A 2024 review stated that developmental and epileptic encephalopathy is mainly driven by genetic factors, typically onset in infancy or early childhood, and generally has a poor prognosis. A 2025 review noted that although individually rare, developmental and epileptic encephalopathies constitute a sizeable group of paediatric epilepsies and emphasised recognising treatable or modifiable entities.
A 2015 article on epileptic encephalopathies discussed the hypothesis that cognitive and developmental outcomes result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent seizures and epileptiform discharges, but presented this as an assumption requiring further evidence. Across these abstracts, no controlled trial data are reported for any drug in developmental and epileptic encephalopathy. What remains missing are prospective trials that stratify patients by specific genetic aetiologies, standardised outcome measures for development beyond seizure counts, and funding for such trials given the rarity of each individual DEE subtype.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2015 · 248 citations · open access
<i>SCN2A</i> encephalopathy
AbstractOBJECTIVE: De novo SCN2A mutations have recently been associated with severe infantile-onset epilepsies. Herein, we define the phenotypic spectrum of SCN2A encephalopathy. METHODS: Twelve patients with an SCN2A epileptic encephalopathy underwent electroclinical phenotyping. RESULTS: Patients were aged 0.7 to 22 years; 3 were deceased. Seizures commenced on day 1-4 in 8, week 2-6 in 2, and after 1 year in 2. Characteristic features included clusters of brief focal seizures with multiple hourly (9 patients), multiple daily (2), or multiple weekly (1) seizures, peaking at maximal frequency within 3 months of onset. Multifocal interictal epileptiform discharges were seen in all. Three of 12 patients had infantile spasms. The epileptic syndrome at presentation was epilepsy of infancy with migrating focal seizures (EIMFS) in 7 and Ohtahara syndrome in 2. Nine patients had improved seizure control with sodium channel blockers including supratherapeutic or high therapeutic phenytoin levels in 5. Eight had severe to profound developmental impairment. Other features included movement disorders (10), axial hypotonia (11) with intermittent or persistent appendicular spasticity, early handedness, and severe gastrointestinal symptoms. Mutations arose de novo in 11 patients; paternal DNA was unavailable in one. CONCLUSIONS: Review of our 12 and 34 other reported cases of SCN2A encephalopathy suggests 3 phenotypes: neonatal-infantile-onset groups with severe and intermediate outcomes, and a childhood-onset group. Here, we show that SCN2A is the second most common cause of EIMFS and, importantly, does not always have a poor developmental outcome. Sodium channel blockers, particularly phenytoin, may improve seizure control.
Epileptic encephalopathies: Optimizing seizure control and developmental outcome
AbstractCognitive and developmental outcomes in patients with epileptic encephalopathy are hypothesized to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent and repetitive seizures and epileptiform discharges that often straddle the interictal and ictal boundaries. This article briefly reviews the evidence related to this assumption, presents critical questions that need to be answered to clarify this relationship, and advances a set of concrete steps that may help improve developmental patient outcomes.
Frontiers in Neurology · 2022 · 13 citations · open access
Solute carrier transporter disease and developmental and epileptic encephalopathy
AbstractThe International League Against Epilepsy officially revised its classification in 2017, which amended "epileptic encephalopathy" to "developmental and epileptic encephalopathy". With the development of genetic testing technology, an increasing number of genes that cause developmental and epileptic encephalopathies are being identified. Among these, solute transporter dysfunction is part of the etiology of developmental and epileptic encephalopathies. Solute carrier transporters play an essential physiological function in the human body, and their dysfunction is associated with various human diseases. Therefore, in-depth studies of developmental and epileptic encephalopathies caused by solute carrier transporter dysfunction can help develop new therapeutic modalities to facilitate the treatment of refractory epilepsy and improve patient prognosis. In this article, the concept of transporter protein disorders is first proposed, and nine developmental and epileptic encephalopathies caused by solute carrier transporter dysfunction are described in detail in terms of pathogenesis, clinical manifestations, ancillary tests, and precise treatment to provide ideas for the precise treatment of epilepsy.
International Journal of Epilepsy · 2025 · 1 citations · open access
Developmental and Epileptic Encephalopathies: Progress in Understanding and Clinical Implications
AbstractAbstract Developmental and epileptic encephalopathies (DEEs) are a group of complex pediatric epilepsies associated with adverse neurodevelopmental outcomes and multiaxial neurological morbidities. The understanding of DEE has evolved from its initial genetic underpinnings, to a clinically driven term encompassing a broader group of etiologies. Although individually rare, the DEEs constitute a sizeable group of pediatric epilepsies. It is especially important to recognize treatable or modifiable entities in this group. This review attempts to highlight the progress in understanding, along with the evolution of the conceptual framework of DEEs. A summary of the currently well-established DEE syndromes is provided along with available precision therapies, which might help the treating physician in the appropriate evaluation and management of the affected children.
Brain and Development Case Reports · 2024 · 1 citations · open access
SCN2A developmental and epileptic encephalopathy in an infant with bilateral polymicrogyria and opercular dysplasia
AbstractSCN2A mutations have been associated with a wide phenotypic spectrum that includes, among others, developmental and epileptic encephalopathy (DEE), usually not associated with any brain structural counterpart. We report the occurrence of a super-refractory status epilepticus (SRSE) in a 2-month-old infant, who presented at birth with refractory neonatal seizures attributed to an extensive bilateral polymicrogyria and cortical dysplasia. Upon his SRSE, he responded radically to the sodium-channel blocker phenytoin with complete seizure resolution and has remained seizure free during the 2-year follow-up period. A SCN2A pathogenic variant was found with predicted gain-of-function effect. Notably, brain MRI findings during the neonatal ictal phase showed signs of hypoxia with cytotoxic and vasogenic oedema, corresponding to the ictal localisation. These changes were not observed upon repetition of the brain MRI during the SRSE at 2 months of age, perhaps suggesting increased neonatal vulnerability to hypoxia in the presence of an SCN2A variant, that modifies over time. Our case report highlights the importance of challenging our clinical management in the presence of refractory seizures attributed solely to a structural cause, with genetic testing providing a key insight for therapeutic management.
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.
DOAJ (DOAJ: Directory of Open Access Journals) · 2024 · 0 citations
Research progress on developmental and epileptic encephalopathy
AbstractDevelopmental and epileptic encephalopathy (DEE) is a group of heterogeneous disorders characterized by drug-resistant seizures and neurodevelopmental delay, which can hinder brain development and lead to severe cognitive, behavioral, and motor impairments. DEE is mainly driven by genetic factors, typically with an onset in infancy or early childhood and generally with an overall poor prognosis. This article provides a review of the definition, epilepsy syndromes, genetic etiology, and precision treatment of DEE.
Therapeutic effect observation of Methylprednisolone for epileptic encephalopathy with epileptic spasms after other antiepileptic medicines were failure
AbstractObjective
To discuss the efficacy and safety of Methylprednisolone therapy to treat epileptic encephalopathy with epileptic spasms after other antiepileptic medicines failed.
Methods
Fifty-eight children with epilepsy seizures were confirmed by video-electroencephalogram(video-EEG) or EEG, and they were given large dose of Vitamin B6 to exclude Vitamin B6 dependent diseases.In addition, they were given large dose of Methylprednisolone therapy for 5 days and treated with prednisone for 8 to 12 weeks.Finally, the followed-ups were performed after patients were treated for 1 week, 1 month, 3 months, 6 months, and 12 months.
Results
The effective percentages of treatment corresponded with Methylprednisolone therapy, including the effective control rate of 86.21% and seizure-free of 34.48% of them at 1 week.At 1 month, the effective rate was 72.41% and 31.03% of the patients with seizure-free.The effective rate was 63.79%, control rate was 32.76% at 3 months.At 6 months, the effective control rate was 65.52%, and control rate was 29.31%.Due to the different duration of hospitalization, 24 children were followed up after 12 months and 62.50% of the patients responded to the large dose of Methylprednisolone therapy, including seizure-free in 33.33% of them.Twenty-three children, whose Adrenocorticotropic hormone treatment failed, then received Methylprednisolone therapy and the effective rate were 65.22%, 52.17%, 47.83%, 47.83% at 1 week, 1 month, 3 months, and 6 months, and the corresponding control rates were 21.74%, 17.39%, 17.39%, 21.74%.The side effects of 58 children spasms were irritation, crying, sleeping more, pressure elevating slightly during therapy.The symptoms disappeared after 1 week.Central obesity was found in 3 cases in 1 to 2 months after the treatment, then they recovered gradually after hormone discontinued.Other adverse reactions were not found in 12 months.
Conclusions
Methylprednisolone therapy is efficient and safe for epileptic spasms, it could be applied to the children who cannot be controlled by other antiepileptic medicines.
Key words:
Epileptic spasms; Methylprednisolone; Therapeutic effect
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.
