DeCure for Developmental and epileptic encephalopathy, 65
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 65 — 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, 65 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, 65 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 2015 review states that cognitive and developmental outcomes in epileptic encephalopathy are thought to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent seizures and epileptiform discharges. It poses critical questions about this relationship and proposes steps to improve developmental outcomes, but provides no trial data, no patient numbers, and no specific drug results.
A 2016 study used in silico prioritisation based on brain gene coexpression to rank 179 candidate genes for epileptic encephalopathy. Five of six subsequently validated candidate genes were among the 19 prioritised in 2013 (odds ratio 54, 95% confidence interval [7,∞], p = 4.5 × 10⁻⁵). The approach was then applied genome-wide, yielding 297 genes ranked in the top 10% for both adult and developing brain coexpression with a reference set of 51 established genes. Nine of those 297 had already been implicated in epileptic encephalopathies: FBXO41, PLXNA1, ACOT4, PAK6, GABBR2, YWHAG, NBEA, KNDC1, and SELRC1. No survival or response rates are reported.
A 2025 review describes developmental and epileptic encephalopathies (DEEs) as a group of complex paediatric epilepsies with adverse neurodevelopmental outcomes and multiaxial neurological morbidities. It notes that understanding has evolved from initial genetic underpinnings to a broader clinical term, and that although individually rare, DEEs constitute a sizeable group. The review highlights the importance of recognising treatable or modifiable entities and provides a summary of well-established DEE syndromes along with available precision therapies. No concrete numbers on survival, response rates, or sample sizes are given.
A 2024 review defines DEE as a heterogeneous group of disorders characterised by drug-resistant seizures and neurodevelopmental delay, driven mainly by genetic factors with onset in infancy or early childhood and generally poor prognosis. It reviews definition, epilepsy syndromes, genetic aetiology, and precision treatment. No specific drug efficacy data, response rates, or survival figures are reported. What remains missing across these publications is any randomised controlled trial data for a repurposed drug in DEE, a standardised patient stratification method, and dedicated funding to test candidate genes or precision therapies in prospective clinical studies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
Neurology Genetics · 2016 · 22 citations · open access
In silico prioritization based on coexpression can aid epileptic encephalopathy gene discovery
AbstractOBJECTIVE: To evaluate the performance of an in silico prioritization approach that was applied to 179 epileptic encephalopathy candidate genes in 2013 and to expand the application of this approach to the whole genome based on expression data from the Allen Human Brain Atlas. METHODS: PubMed searches determined which of the 179 epileptic encephalopathy candidate genes had been validated. For validated genes, it was noted whether they were 1 of the 19 of 179 candidates prioritized in 2013. The in silico prioritization approach was applied genome-wide; all genes were ranked according to their coexpression strength with a reference set (i.e., 51 established epileptic encephalopathy genes) in both adult and developing human brain expression data sets. Candidate genes ranked in the top 10% for both data sets were cross-referenced with genes previously implicated in the epileptic encephalopathies due to a de novo variant. RESULTS: Five of 6 validated epileptic encephalopathy candidate genes were among the 19 prioritized in 2013 (odds ratio = 54, 95% confidence interval [7,∞], p = 4.5 × 10(-5), Fisher exact test); one gene was false negative. A total of 297 genes ranked in the top 10% for both the adult and developing brain data sets based on coexpression with the reference set. Of these, 9 had been previously implicated in the epileptic encephalopathies (FBXO41, PLXNA1, ACOT4, PAK6, GABBR2, YWHAG, NBEA, KNDC1, and SELRC1). CONCLUSIONS: We conclude that brain gene coexpression data can be used to assist epileptic encephalopathy gene discovery and propose 9 genes as strong epileptic encephalopathy candidates worthy of further investigation.
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.
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.
Seizure control in glycine encephalopathy using the Ketamine-Dextromethorphan-Sodium benzoate triple therapy
AbstractNeonatal glycine encephalopathy is a rare genetic neurometabolic disorder secondary to glycine cleavage system deficiency. Patients typically present with early-onset intractable seizures, status epilepticus and encephalopathy. Seizures control remains challenging in view of their refractoriness to standard anti-seizure medications. Sodium benzoate is commonly used to control the elevated glycine level. Oral anti-NMDA receptor antagonists, ketamine and dextromethorphan, have been used in various combinations in the treatment of this complex disorder. In this report, we present a neonatal case of classical glycine encephalopathy with hypotonia and refractory myoclonic seizures. The status epilepticus was successfully treated using a combination of intravenous ketamine, oral dextromethorphan and sodium benzoate. Seizures resolved and the patient's development showed improvement on follow-up. The intravenous form of ketamine in the neonatal period is rarely used, and it has been reported in only two glycine encephalopathy patients in the literature. This is the first report in the literature of the efficacy of intravenous ketamine using the above triple therapy. This intervention might have implications on the management of neonatal intractable seizures in glycine encephalopathy, which might improve the outcome of this devastating disorder.
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.
