DeCure for Developmental and epileptic encephalopathy, 52
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 52 — 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, 52 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
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, 52 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
sodium voltage-gated channel beta subunit 1 (SCN1B) — SCN1B 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 rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7W9K · 2.2 Å · ligand O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine (P5S). Experimental structure, not a prediction.
What the evidence adds up to
Developmental and epileptic encephalopathies are a group of rare, severe early-onset epilepsies defined by drug-resistant seizures, marked electroencephalographic abnormalities, and delayed or regressive psychomotor development. The disorders are mainly driven by genetic factors and are associated with poor long-term outcomes and increased mortality. Comorbidities include intellectual disability, psychiatric disorders, motor dysfunction, and respiratory and gastrointestinal problems. Most antiseizure drugs are ineffective; treatments that are effective often entail significant risk and cost. A systematic review of cannabidiol in children with these conditions included 13 studies and 656 children. Cannabidiol was administered at a maximum dose of 50 mg/kg/day. In 10 of those studies, at least 20% of patients experienced a reduction of 50% or more in seizure frequency. Adverse events were relatively common and included somnolence, loss of appetite, diarrhoea, fatigue, and increased serum aminotransferases; most were mild to moderate and reversible.
Next-generation sequencing technologies have revolutionised the identification of single-gene causes but have had only a modest impact on patient-specific treatment decisions. Treatment remains driven chiefly by electroclinical syndrome classification. Early recognition and targeted treatment can impact neurodevelopmental outcomes, and the approach is evolving to include repurposed antiseizure medications, targeted therapies, and early surgical intervention in select patients. A significant minority of patients respond to, or are even cured by, specific therapies, but most patients experience very poor outcomes. None of the currently available drugs have succeeded in suppressing epileptiform activity in these conditions.
The pathogenesis involves a complex interplay of genetic factors, neurobiological mechanisms, and environmental influences. Emerging therapies such as gene and stem cell therapy are under discussion but remain at an early stage. The long-term effects of cannabidiol on development and quality of life have not been investigated. Multidisciplinary care is considered paramount, but the evidence base for most management decisions remains thin.
What is still missing are adequately powered randomised trials that stratify patients by genetic aetiology, long-term follow-up data on neurodevelopmental outcomes beyond seizure counts, and funding for the kind of precision medicine that the genetic findings might eventually support. The gap between genetic diagnosis and effective treatment has not been closed.
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.
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.
CONTINUUM Lifelong Learning in Neurology · 2018 · 15 citations
Epileptic Encephalopathies
AbstractPURPOSE OF REVIEW: This article reviews the manifestations and treatment of the epileptic encephalopathies, which are a heterogeneous group of disorders characterized by both seizures and neurocognitive impairment. RECENT FINDINGS: Next-generation (exome- and genome-based) sequencing technologies are revolutionizing the identification of single-gene causes of epileptic encephalopathy but have only had a modest impact on patient-specific treatment decisions. The treatment of most forms of epileptic encephalopathy remains a particularly challenging endeavor, with therapeutic decisions chiefly driven by the electroclinical syndrome classification. Most antiseizure drugs are ineffective in the treatment of these disorders, and treatments that are effective often entail significant risk and cost. SUMMARY: The epileptic encephalopathies continue to pose a major challenge in diagnosis and treatment, with most patients experiencing very poor outcomes, although a significant minority of patients respond to, or are even cured by, specific therapies.
Frontiers in Pediatrics · 2022 · 9 citations · open access
A Treatable Genetic Disease Caused by CAD Mutation
AbstractType 50 early infantile epileptic encephalopathy, or EIEE-50 for short, is an autosomal recessive genetic disorder resulting from CAD mutations. So far, little has been reported on the disease. In this article, we will discuss the case of a male infant who is 8 years and 5 months old. A whole-exome sequencing of the boy revealed CAD compound heterozygous mutations. He suffered from global developmental delay and regression, refractory epilepsy, and anemia. After his diagnosis, we used uridine treatment and gained encouraging results. In this article, we will analyze our case studies in the context of the literature, so as to improve pediatricians' understanding of the disease.
Management of Developmental and Epileptic Encephalopathies
AbstractDevelopmental and epileptic encephalopathies (DEEs) are a group of rare, severe, early-onset epilepsies characterized by pharmacoresistance, marked electroencephalographic abnormalities, and delayed or regressive psychomotor development. DEEs are associated with poor long-term outcomes and increased mortality; however, early recognition and targeted treatment can impact neurodevelopmental outcomes and overall quality of life. Treatment with antiseizure medication is often challenging given drug resistance, chronic polypharmacy, and medication interactions. With advances in genetic testing and increased understanding of the neurobiological mechanisms of DEEs, the treatment approach is evolving and includes repurposed antiseizure medications and targeted therapies, as well as early surgical intervention in select patients. In addition to high seizure burden and neurodevelopmental delay, DEEs are associated with comorbidities affecting a range of body systems; these can include intellectual disability, psychiatric disorders, motor dysfunction, and respiratory and gastrointestinal problems. Over time, these comorbidities increase the complexity of management and have important implications on the disease burden and quality of life for both patients and their caregivers. Multidisciplinary care in DEEs is paramount. We summarize the current evidence on the management of specific DEEs, focusing on targeted therapies and optimizing outcomes.
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.
Aristotle University of Thessaloniki · 2025 · 0 citations · open access
Efficacy and safety of cannabidiol in children with developmental and epileptic encephalopathies: A systematic review
AbstractDevelopmental and epileptic encephalopathies constitute rare epileptic conditions characterized by treatment-resistant seizures, neurodevelopmental delays, and various comorbidities. None of the currently available drugs succeeded in suppressing the epileptiform activity in those conditions. Cannabidiol has been used as a novel treatment strategy in patients with treatment-resistant epilepsies. We aimed to assess the efficacy and safety of cannabidiol in children with developmental and epileptic encephalopathies through a systematic review. For this systematic review, we searched MEDLINE, Cochrane Central Register of Controlled Trials, trial registries, and reference lists of included studies. All types of studies of pharmaceutical cannabidiol in children with developmental and epileptic encephalopathies were eligible, and we did not set any language or date restrictions. The risk of bias in included studies was assessed using validated tools. Of the 683 records identified, 13 were eligible for inclusion in this review. Studies were of different types and included a total of 656 children with developmental and epileptic encephalopathies. Cannabidiol was administered at a maximum 50mg/kg/day dose. Almost all studies reported positive outcomes with cannabidiol, leading to a reduction of 50% or above in seizure frequency in at least 20% of patients included in 10 studies. Adverse events were relatively common across studies and included somnolence, loss of appetite, diarrhea, fatigue, and increased serum aminotransferases. Most of them were mild to moderate and reversible. Overall, cannabidiol was found to be well tolerated and to effectively reduce seizure frequency in children with developmental and epileptic encephalopathies experiencing seizures uncontrolled with concomitant antiepileptic medications. Future research should investigate the long-term effects of cannabidiol not only in seizure control but also in enhancing the development and quality of life of affected children.
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.
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.
