DeCure for Developmental and epileptic encephalopathy, 46
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 46 — 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 moduleDevelopmental and epileptic encephalopathy, 46 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 developmental and epileptic encephalopathy, 46 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
glutamate ionotropic receptor NMDA type subunit 2D (GRIN2D) — GRIN2D 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 glydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9D37 · 3.34 Å · ligand GLYCINE (GLY). Experimental structure, not a prediction.
What the evidence adds up to
Developmental and epileptic encephalopathy (DEE) is defined by cognitive impairment driven by both seizures and the underlying neurobiological process, with onset typically in early childhood. Many cases are linked to gene variants. The 2021 review distinguishes DEE from epileptic encephalopathy (EE), where cognition is directly harmed by epileptic activity and may improve with aggressive treatment, and from developmental encephalopathy (DE), where epileptiform activity has minimal effect on function and aggressive antiseizure medication is unlikely to help. The review states that patients with DEE might benefit from a precision medicine approach to reduce the overall burden of epilepsy, but provides no trial data.
A 2024 retrospective study of 21 paediatric patients with EE treated with pulse intravenous methylprednisolone (IVMP) reported a responder rate (seizure reduction greater than 50%) of 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic aetiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy (p=0.0475). The fourth month of therapy was the minimum time point to establish effectiveness. All patients showed improvements in quality of life, EEG tracing and postural-motor development. No relevant adverse events were observed. The study is small, retrospective, and uncontrolled.
Earlier literature is more cautious. A 2013 review states that diagnostic criteria for epileptic encephalopathy are not well developed and treatment options are very limited, so patients cannot receive adequate treatment, which further aggravates the encephalopathy. A 2006 case report describes a child whose focal epilepsy evolved from treatment-responsive to treatment-resistant with an epileptic encephalopathy between 18 months and 3 years, illustrating poorly understood age-related changes in seizure susceptibility and drug responsiveness. No data exist for any drug specifically in DEE-46. What is missing are prospective trials with genetic stratification, larger sample sizes, and funding to test whether the IVMP response seen in a mixed EE cohort holds for defined DEE subtypes.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Epileptic Disorders · 2021 · 126 citations · open access
Developmental and epileptic encephalopathies: recognition and approaches to care
AbstractThe term "developmental and epileptic encephalopathy" (DEE) refers to when cognitive functions are influenced by both seizure and interictal epileptiform activity and the neurobiological process behind the epilepsy. Many DEEs are related to gene variants and the onset is typically during early childhood. In this setting, neurocognition, whilst not improved by seizure control, may benefit from some precision therapies. In patients with non-progressive diseases with cognitive impairment and co-existing epilepsy, in whom the epileptiform activity does not affect or has minimal effect on function, the term "developmental encephalopathy" (DE) can be used. In contrast, for those patients with direct impact on cognition due to epileptic or epileptiform activity, the term "epileptic encephalopathy" (EE) is preferred, as most can revert to their normal or near normal baseline cognitive state with appropriate intervention. These children need aggressive treatment. Clinicians must tailor care towards individual needs and realistic expectations for each affected person; those with DE are unlikely to gain from aggressive antiseizure medication whilst those with EE will gain. Patients with DEE might benefit from a precision medicine approach in order to reduce the overall burden of epilepsy.
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.
Efficacy and Safety of Pulse Intravenous Methylprednisolone in Pediatric Epileptic Encephalopathies: Timing and Networks Consideration
AbstractAbstract: Background: epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early-onset, and unfavorable developmental outcome. We describe a cohort of pediatric patients with EE who underwent intravenous methylprednisolone (IVMP) pulse therapy to examine its efficacy/tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were: ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction >50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of Life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: Twenty-one patients were included. The responding rate was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic etiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy (p=0.0475). The fourth month of therapy was the minimum time point to establish the effectiveness of the treatment. All patients showed improvements in QoL, EEG tracing and postural-motor development. No relevant adverse events were observed. Conclusions: Our study confirms the efficacy and tolerability of pulse IVMP treatment in pediatric patients with EE, especially with genetic etiology and ESES. The fourth month of therapy was the minimum time point to establish its effectiveness. QoL, EEG and postural-motor development also showed improvement.
NATIONAL JOURNAL OF NEUROLOGY · 2013 · 0 citations · open access
On the Clinics and Diagnosis of Epileptic Encephalopathy
AbstractEarly childhood is characterized by a continuous process of development of structures and functions of organism, especially central nervous system.The concept of epileptic encephalopathy is based on the assumption that the aggressive epileptic activity during the maturation of the brain is the main causal factor in cognitive and neuropsychological impairment or regress. With age, EEG signs of evolving consistent with the transition into each another. Currently the diagnosis criteria are not well developed and the treatment options are very limited, whereby patients cannot receive adequate treatment that further aggravates encephalopathy. Unfortunately clinicians are often unable to diagnose also benign epileptic syndromes.
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.
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.
