DeCure for Developmental and epileptic encephalopathy, 86
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 86 — screening already-approved drugs against its 2-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, 86 maps to a 2-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
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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, 86 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.
What the evidence adds up to
The term developmental and epileptic encephalopathy (DEE) describes a group of paediatric epilepsies where cognitive impairment arises from both the underlying genetic or neurobiological cause and the epileptic activity itself. A 2021 review distinguishes DEE from developmental encephalopathy (DE), where epileptiform activity has minimal effect on function and aggressive antiseizure medication is unlikely to help, and from epileptic encephalopathy (EE), where cognition is directly impaired by seizures and can often return to near-baseline with appropriate intervention. Many DEEs are linked to gene variants; by August 2022, 105 genes had been associated with DEE according to OMIM. A 2023 study of patients at a reference centre in Northeast Brazil confirms that genetic factors are a major cause. A 2025 review notes that although individually rare, DEEs constitute a sizeable group of paediatric epilepsies and that treatable or modifiable entities should be recognised.
A 2024 retrospective study of 21 paediatric patients with EE who received pulse intravenous methylprednisolone (IVMP) therapy 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 retrospective, includes only 21 patients, and does not report long-term cognitive outcomes beyond the 6-month post-therapy follow-up.
A 2024 comprehensive review on EE summarises that current therapeutic strategies include pharmacological treatments, nonpharmacological interventions, and emerging therapies such as gene and stem cell therapy. The review states that significant challenges and limitations remain and that ongoing research is needed. It does not provide new data on any specific drug. The 2021 review notes that patients with DEE might benefit from a precision medicine approach to reduce the overall burden of epilepsy, but no concrete efficacy data for any precision therapy is given in these abstracts.
What is still missing are large, prospective, controlled trials for any drug in DEE or EE, including IVMP. The existing IVMP data come from a single-centre retrospective study with a small sample and no control group. Patient stratification by genetic aetiology and EEG pattern (ESES) may be important, but validated biomarkers to predict response are lacking. Funding for multi-centre trials and for the development of gene-specific therapies remains insufficient.
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.
Estado epiléptico eléctrico durante el sueño: estudio retrospectivo multicéntrico de 29 casos
AbstractINTRODUCTION: Electrical status epilepticus during sleep (ESES) is an epileptic syndrome characterised by the presence of very persistent slow spike-wave-type epileptic discharges during non-REM sleep. The management of this pathology, today, is heterogeneous and no controlled studies have been conducted with the treatments employed; similarly, whether or not they improve patients' cognitive development or not has still to be determined. PATIENTS AND METHODS: A review was carried out of the patients diagnosed with ESES at four hospitals over a period of 15 years; data concerning their clinical presentation, therapeutic management and clinical course were collected and compared with the literature. RESULTS: Altogether 29 patients with ESES were detected, 20 of them idiopathic and 26 generalised. The drugs with which the greatest control of the electrical activity was achieved were corticoids/adrenocorticotropic hormone (ACTH), clobazam and levetiracetam. In the primary cases ESES lasted an average of six months and the duration was twice that time in the secondary cases. Findings showed that the intelligence quotient remained normal in 45% of patients and 40% presented differing degrees of cognitive disability in the course of the pathology. CONCLUSIONS: The developmental neuropsychological prognosis is usually unfavourable and the cognitive development seems to be related with the duration of ESES and the area where the epileptic activity is concentrated, which suggests that the poor prognosis can be avoided if treatment is established at an early stage. The antiepileptic drugs that are most commonly used are valproic acid, ethosuximide and levetiracetam, and in our milieu clobazam and lamotrigine were commonly employed. The most effective drugs for controlling ESES were corticoids/ACTH, clobazam and levetiracetam.
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.
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.
BMJ Case Reports · 2024 · 1 citations · open access
Hyperammonemic encephalopathy induced by valproic acid
AbstractValproate (VPA) is broad-spectrum antiepileptic drug. Several adverse reactions including hepatotoxicity, fetal risk and pancreatitis are well known and labelled as boxed warnings in the USA. One adverse reaction that is less well known but clinically significant for its severe morbidity is hyperammonemic encephalopathy. We present a case of woman with hyperammonemic encephalopathy following the initiation of VPA therapy; she had a favourable outcome with discontinuation of the drug and prompt treatment with lactulose and L-carnitine.
A Comprehensive Review on Current Insights Into Epileptic Encephalopathy: Pathogenesis and Therapeutic Strategies
AbstractEpileptic encephalopathy (EE) represents a challenging group of disorders characterized by severe epilepsy and significant cognitive, behavioral, and neurological impairments. This comprehensive review aims to elucidate the current insights into the pathogenesis and therapeutic strategies for these disorders. Pathogenesis involves a complex interplay of genetic factors, neurobiological mechanisms, and environmental influences that contribute to the severity and progression of symptoms. Clinical manifestations are diverse, encompassing various seizure types, cognitive and behavioral impairments, and developmental delays. Current therapeutic strategies include pharmacological treatments, nonpharmacological interventions, and emerging therapies such as gene and stem cell therapy. Despite advancements, significant challenges and limitations remain, highlighting the need for ongoing research and innovation. This review synthesizes existing knowledge, identifies research gaps, and proposes future directions, emphasizing the potential for personalized medicine to improve patient outcomes and quality of life.
Arquivos de Neuro-Psiquiatria · 2023 · 0 citations · open access
Genetic profile of patients with developmental and epileptic encephalopathy at a reference center in Northeast Brazil
AbstractBackground: The developmental and epileptic encephalopathy (DEE) diseases where there is developmental impairment related to both the underlying etiology independent of epileptiform activity and the epileptic encephalopathy. Many DEEs have a genetic basis that, by themselves, can alter the neurodevelopmental delay. By August 2022, there were 105 genes associated with DEE according to OMIM.
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.
