DeCure for Developmental and epileptic encephalopathy, 12
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 12 — 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 moduleDevelopmental and epileptic encephalopathy, 12 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
Structures already discussed alongside developmental and epileptic encephalopathy, 12 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
sodium voltage-gated channel alpha subunit 2 (SCN2A) — SCN2A is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has (3beta,14beta,17beta,25r)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en bound in it, shown as sticks.
Loading structure…
helix sheet 3beta,14beta,17beta,25rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6J8E · 3.0 Å · ligand (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en (9Z9). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts do not describe a specific drug or treatment for developmental and epileptic encephalopathy type 12. They instead discuss the conceptual distinction between epileptic encephalopathy and developmental encephalopathy. The 2018 review defines epileptic encephalopathy as a process of neurological impairment caused by the epileptic activity itself, which is potentially reversible with successful treatment, though to a variable extent. Developmental encephalopathy, by contrast, applies when epilepsy and developmental delay both stem from the underlying aetiology, and aggressive antiepileptic treatment may not be helpful. The 2015 article states that cognitive and developmental outcomes are hypothesised to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent seizures and epileptiform discharges. The 2006 case report describes a child whose treatment-responsive focal epilepsy evolved into treatment-resistant focal epilepsy with an epileptic encephalopathy between 18 months and 3 years, illustrating poorly understood age-related changes in seizure susceptibility, seizure types, and drug responsiveness.
No concrete numbers for survival, response rates, or sample sizes are given in any of these abstracts. No drug is named. The 2018 review notes that further research is needed to elucidate underlying pathophysiological mechanisms, define clear outcome predictors, and find new treatment targets. The 2015 article advances a set of concrete steps that may help improve developmental patient outcomes but does not specify what those steps are.
What is still missing for this specific disease is any clinical trial data, any identified drug, any patient stratification strategy, and any funding directed at the type 12 genetic subtype. The abstracts provide only a framework for thinking about the condition, not evidence for any intervention.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Medicine Science and the Law · 1964 · 119 citations
The Neuropathology of Status Epilepticus
AbstractA description is given of the clinical and neuropathological findings in eleven cases of status epilepticus in young children. The distribution of ischaemic nerve cell changes in cerebral cortex, hippocampus, basal ganglia, and cerebellum, conform to the pattern of post-ictal brain damage described by Scholz. The same changes are found in brains showing oedema as in those without. Reasons are given for discounting the theory that vascular compression plays a decisive part in the pathogenesis of this type of encephalopathy.
Epileptic Disorders · 2011 · 53 citations · open access
The efficacy of bromides, stiripentol and levetiracetam in two patients with malignant migrating partial seizures in infancy
AbstractThe syndrome of malignant migrating partial seizures in infancy is a devastating, age-specific, epileptic encephalopathy, which still presents an aetiological, pathophysiological and therapeutic problem. In this study, we present two patients who were diagnosed with the disease, based on electroclinical symptoms. The patients were treated with a combination of sodium bromide, stiripentol and levetiracetam. The first patient unequivocally responded, following a course of ineffective conventional drugs, and the second, who was diagnosed and treated immediately, showed a more significant therapeutic response. Antiepileptic drugs, previously reported to be beneficial in case reports, when given concomitantly, may substantially reduce the number and severity of seizures, without influence on psychomotor development. [Published with video sequences].
Current Opinion in Neurology · 2018 · 49 citations · open access
The epileptic encephalopathy jungle – from Dr West to the concepts of aetiology-related and developmental encephalopathies
AbstractPURPOSE OF REVIEW: We aim to further disentangle the jungle of terminology of epileptic encephalopathy and provide some insights into the current understanding about the aetiology and pathophysiology of this process. We cover also the key features of epilepsy syndromes of infancy and childhood which are considered at high risk of developing an epileptic encephalopathy. RECENT FINDINGS: The concept of 'epileptic encephalopathy' has progressively been elaborated by the International League Against Epilepsy according to growing clinical and laboratory evidence. It defines a process of neurological impairment caused by the epileptic activity itself and, therefore, potentially reversible with successful treatment, although to a variable extent. Epileptic activity interfering with neurogenesis, synaptogenesis, and normal network organization as well as triggering neuroinflammation are among the possible pathophysiological mechanisms leading to the neurological compromise. This differs from the newly introduced concept of 'developmental encephalopathy' which applies to where the epilepsy and developmental delay are both because of the underlying aetiology and aggressive antiepileptic treatment may not be helpful. SUMMARY: The understanding and use of correct terminology is crucial in clinical practice enabling appropriate expectations of antiepileptic treatment. Further research is needed to elucidate underlying pathophysiological mechanisms, define clear outcome predictors, and find new treatment targets.
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.
Rufinamide in children and adults in routine clinical practice
AbstractOBJECTIVE: To explore the long-term effectiveness of rufinamide in managing Lennox-Gastaut Syndrome (LGS), other epileptic encephalopathies, and intractable focal epilepsies in adults and children in routine clinical practice. METHODS: A multicentre, retrospective chart review of patients prescribed adjunctive rufinamide at seven Spanish epilepsy centres, with assessments at six and 12 months. RESULTS: We evaluated data from 58 patients (40 male, age range 7-57 years), 25 of whom were diagnosed with LGS, 12 with other epileptic encephalopathies and 21 of whom were diagnosed with focal epilepsies, mainly frontal lobe. The mean daily rufinamide dose was 32.0 mg/kg (range 12.5-66.7 mg/kg) in children and 24.7 mg/kg (range 5.0-47.0 mg/kg) in adults, and the most commonly used concomitant antiepileptic drugs were levetiracetam and valproate. Rufinamide was discontinued in 25 patients (43.1%) during the 1-year follow-up, and the most common reason was lack of effectiveness (n = 12, 20.7% of total). The frequency of generalized tonic-clonic seizures was significantly reduced from baseline at 6 and 12 months (P = 0.001), both in patients with generalized epilepsies and in patients with focal epilepsies. Significant seizure frequency reduction from baseline was observed at 12 months (P = 0.01) for tonic/atonic seizures and at 6 months (P = 0.001) for focal seizures. Side effects were reported in 21 patients (36.2%): nausea, vomiting and weight loss were most frequent. CONCLUSIONS: Rufinamide was well tolerated and was effective in reducing frequency of generalized tonic-clonic, tonic/atonic and focal seizures in both children and adults with severe refractory epilepsies, primarily LGS.
A Child with Epilepsy: Initial Presentation and Subsequent Course
AbstractPresented is the case of a child with epilepsy with dramatic evolution between the ages of 18 months and 3 years. Initially, the case is one of treatment-responsive focal epilepsy, but then evolves to treatment-resistant focal epilepsy with an epileptic encephalopathy. The case demonstrates the poorly understood entities of age-related changes in seizure suspectibility, seizure types, and drug responsiveness.
CACNA1A-associated epileptic encephalopathy triggered by minor trauma: importance of early diagnosis and appropriate treatment
AbstractThis case describes a female toddler who presented with status epilepticus, altered sensorium and hemiparesis after a trivial trauma, initially raising suspicion for acute ischaemic stroke. However, genetic analysis identified a novel heterozygous CACNA1A mutation, confirming developmental and epileptic encephalopathy. The child was subsequently started on targeted therapy with flunarizine, acetazolamide and antiepileptic medications, which led to effective seizure control and neurological improvement. This case emphasises the need to consider CACNA1A-associated encephalopathy in children presenting with post-traumatic seizures and encephalopathy, as early diagnosis facilitates individualised treatment and may alter disease trajectory.
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.
