DeCure for Developmental and epileptic encephalopathy, 14
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 14 — 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, 14 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, 14 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
CUGBP Elav-like family member 2 (CELF2) — CELF2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9URH · 1.82 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
The concept of epileptic encephalopathy describes a process of neurological impairment caused by the epileptic activity itself, which is potentially reversible with successful treatment, though to a variable extent. This differs from developmental encephalopathy, where both epilepsy and developmental delay stem from the underlying aetiology and aggressive antiepileptic treatment may not be helpful. The term developmental and epileptic encephalopathy (DEE) now encompasses both mechanisms: developmental impairment related to the underlying aetiology independent of epileptiform activity, plus the epileptic encephalopathy component. By August 2022, 105 genes were associated with DEE according to OMIM. The 2015 Neurobiology of Disease in Children symposium noted that seizures in epileptic encephalopathies are often intractable and multiform, and that there is still a great need for further randomised controlled trials to create clinically effective therapies.
Diagnosis criteria for epileptic encephalopathy are not well developed, and treatment options are very limited, meaning patients cannot receive adequate treatment, which further aggravates the encephalopathy. Clinicians are often unable to diagnose even benign epileptic syndromes. The epileptic activity itself is thought to interfere with neurogenesis, synaptogenesis, and normal network organisation, and to trigger neuroinflammation, as possible pathophysiological mechanisms leading to neurological compromise. With age, EEG signs evolve consistently with the transition into each another syndrome.
No abstract provides any specific drug, treatment, survival, response rate, or sample size data for any therapy in DEE. The 2017 review states that progress has been made toward better treatment options as more is learned about aetiologies, but does not name any drug or report any clinical trial results. The 2018 review notes that correct terminology enables appropriate expectations of antiepileptic treatment, but does not describe any particular treatment outcome.
What is still missing are randomised controlled trials for any therapy in DEE, clear outcome predictors, well-developed diagnostic criteria, and patient stratification by the specific genetic aetiology among the 105 known genes. No abstract reports a successful clinical trial, a specific drug effect, or any quantitative measure of benefit.
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: Clinical Aspects, Molecular Features and Pathogenesis, Therapeutic Targets and Translational Opportunities, and Future Research Directions
AbstractEpileptic encephalopathies encompass a heterogeneous group of epilepsy syndromes that manifest with cognitive, behavioral, and neurologic deficits, seizures that are often intractable and multiform, aggressive electroencephalographic paroxysmal activity, and sometimes early death. As more is learned about the etiologies and manifestations of epileptic encephalopathies, progress has been made toward better treatment options. However, there is still a great need for further randomized controlled trials and research to help create clinically effective therapies. The 2015 Neurobiology of Disease in Children symposium, held in conjunction with the 44th annual meeting of the Child Neurology Society, aimed to (1) describe the clinical concerns involving diagnosis and treatment, (2) review the current status of understanding in the pathogenesis of epileptic encephalopathy, (3) discuss clinical management and therapies for epileptic encephalopathy, and (4) define future directions of research. This article summarizes the presentations and includes an edited transcript of question-and-answer sessions.
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.
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.
