DeCure for Developmental and epileptic encephalopathy 98
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy 98 — 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 98 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 98 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
A single case report describes a 4-month-old girl with intractable epilepsy in whom most antiepileptic drugs were ineffective. High doses of phenytoin suppressed seizures, leading clinicians to suspect a sodium channelopathy. Targeted DNA sequencing revealed a pathogenic missense variant Val1315Met in the SCN8A gene. After diagnosis, combination therapy with sodium channel blockers was initiated and the seizures resolved. The authors note that even when a single sodium channel blocker is insufficient, combination therapy can lead to seizure freedom in SCN8A developmental and epileptic encephalopathy. This is a single case, not a trial.
Two review articles summarise the field. Developmental and epileptic encephalopathies are a group of heterogeneous 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. One review emphasises the importance of recognising treatable or modifiable entities and provides a summary of available precision therapies. The other reviews the definition, epilepsy syndromes, genetic aetiology, and precision treatment of DEE. A separate review focuses on ARX mutations, which cause West syndrome, X-linked infantile spasms, X-linked myoclonic epilepsy with spasticity, and Ohtahara syndrome, noting these are often drug resistant.
No controlled trial data exist for any drug in DEE98 specifically. The single case of SCN8A-DEE treated with combination sodium channel blockers is encouraging but cannot be generalised. What is missing is prospective, controlled trials of combination sodium channel blocker therapy in SCN8A-DEE, systematic patient stratification by specific SCN8A variant, and funding to move from single-case reports to cohort 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.
Epilepsia Open · 2021 · 91 citations · open access
Guidance on Dravet syndrome from infant to adult care: Road map for treatment planning in Europe
AbstractDravet syndrome (DS) is a severe, rare, and complex developmental and epileptic encephalopathy affecting 1 in 16 000 live births and characterized by a drug-resistant epilepsy, cognitive, psychomotor, and language impairment, and behavioral disorders. Evidence suggests that optimal treatment of seizures in DS may improve outcomes, even though neurodevelopmental impairments are the likely result of both the underlying genetic variant and the epilepsy. We present an updated guideline for DS diagnosis and treatment, taking into consideration care of the adult patient and nonpharmaceutical therapeutic options for this disease. This up-to-date guideline, which is based on an extensive review of the literature and culminates with a new treatment algorithm for DS, is a European consensus developed through a survey involving 29 European clinical experts in DS. This guideline will serve professionals in their clinical practice and, as a consequence, will benefit DS patients and their families.
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.
Brain and Development Case Reports · 2024 · 2 citations · open access
A case of SCN8A-related developmental epileptic encephalopathy diagnosed by clinical speculation driven targeted DNA sequencing and remission of epilepsy by sodium channel blockers combination therapy
AbstractSCN8A-related epilepsy and/or neurodevelopmental disorders encompass a very broad spectrum of phenotypes. The most severe form, SCN8A developmental and epileptic encephalopathy (DEE), develops intractable epilepsy from early infancy and can lead to sudden death. Early diagnosis and therapeutic intervention are essential, but diagnosis is based on genetic testing and definitive diagnosis is often delayed. A 4-month-old girl presented with intractable epilepsy. Most antiepileptic drugs were ineffective, but high doses of phenytoin suppressed seizures, so a sodium channelopathy was suspected and targeted DNA sequencing was performed, which revealed a pathogenic missense variant Val1315Met in the SCN8A gene. Based on the diagnosis, combination therapy with sodium channel blockers (SCBs) was initiated and the seizures resolved. We experienced SCN8A-DEE, which led to early diagnosis based on clinical course and improved prognosis. It is noteworthy that even when the effect of a single SCB is insufficient, as in this case, combination therapy can lead to seizure free in SCN8A-DEE.
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.
Journal of Pediatric Neurology · 2021 · 0 citations
Aristaless-Related Homeobox (ARX): Epilepsy Phenotypes beyond Lissencephaly and Brain Malformations
AbstractAbstract The Aristaless-related homeobox (ARX) transcription factor is involved in the development of GABAergic and cholinergic neurons in the forebrain. ARX mutations have been associated with a wide spectrum of neurodevelopmental disorders in humans and are responsible for both malformation (in particular lissencephaly) and nonmalformation complex phenotypes. The epilepsy phenotypes related to ARX mutations are West syndrome and X-linked infantile spasms, X-linked myoclonic epilepsy with spasticity and intellectual development and Ohtahara and early infantile epileptic encephalopathy syndrome, which are related in most of the cases to intellectual disability and are often drug resistant. In this article, we shortly reviewed current knowledge of the function of ARX with a particular attention on its consequences in the development of epilepsy during early childhood.
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.
