DeCure for Developmental and epileptic encephalopathy, 44
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 44 — 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, 44 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, 44 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
ubiquitin like modifier activating enzyme 5 (UBA5) — UBA5 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 atpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6H77 · 2.1 Å · ligand ADENOSINE-5'-TRIPHOSPHATE (ATP). Experimental structure, not a prediction.
What the evidence adds up to
Developmental and epileptic encephalopathy 44 is a rare, severe, early-onset epilepsy characterised by pharmacoresistance, marked electroencephalographic abnormalities, and delayed or regressive psychomotor development. The condition is associated with poor long-term outcomes and increased mortality. Treatment with antiseizure medication is often challenging given drug resistance, chronic polypharmacy, and medication interactions. In addition to high seizure burden and neurodevelopmental delay, DEEs are associated with comorbidities affecting a range of body systems including intellectual disability, psychiatric disorders, motor dysfunction, and respiratory and gastrointestinal problems.
The term 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 with onset typically during early childhood. For patients with direct impact on cognition due to epileptic or epileptiform activity, the term epileptic encephalopathy is preferred, as most can revert to their normal or near normal baseline cognitive state with appropriate intervention. These children need aggressive treatment. Patients with DEE might benefit from a precision medicine approach in order to reduce the overall burden of epilepsy.
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. The review from 2025 summarises current evidence on management of specific DEEs focusing on targeted therapies and optimising outcomes. Another 2025 review attempts to highlight progress in understanding along with evolution of the conceptual framework of DEEs, providing a summary of currently well-established DEE syndromes along with available precision therapies.
What is still missing are large-scale clinical trials for specific DEE subtypes, validated biomarkers to distinguish patients who will benefit from aggressive antiseizure treatment from those who will not, and funding for multidisciplinary care models that address the full range of comorbidities. The evidence base remains limited to small case series and expert opinion, with no randomised controlled trial data for DEE44 specifically. Patient stratification by genetic aetiology is not yet standardised in clinical practice.
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.
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.
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.
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.
Metabolic Diseases with Epilepsy Vitamin Responsive Conditions
AbstractVitamin-responsive metabolic epilepsies are a group of inherited disorders characterized by a specific enzyme deficiency, and not a vitamin deficiency state. Epilepsy is usually present at disease onset, and most patients do not respond to antiepileptic drugs. However, personalized treatment with specific vitamin therapy markedly improves both seizures and encephalopathy.
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.
