DeCure for Developmental and epileptic encephalopathy 109
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy 109 — 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 109 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 109 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
fizzy and cell division cycle 20 related 1 (FZR1) — FZR1 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 9GAW · 2.9 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Developmental and epileptic encephalopathy 109 is one of a group of rare paediatric epilepsies in which seizures and interictal epileptiform activity directly impair cognitive function. Many of these encephalopathies are caused by single-gene variants, and onset is typically in early childhood. A 2021 review notes that neurocognition is not improved by seizure control alone, but may benefit from some precision therapies. The same review distinguishes between developmental encephalopathy, where epileptiform activity has minimal effect on function and aggressive antiseizure medication is unlikely to help, and epileptic encephalopathy, where cognition can revert to near normal with appropriate intervention. Patients with DEE might benefit from a precision medicine approach to reduce the overall burden of epilepsy.
A 2018 review states that next-generation sequencing has revolutionised the identification of single-gene causes of epileptic encephalopathy but has had only modest impact on treatment decisions. Most antiseizure drugs are ineffective in these disorders, and treatments that are effective often entail significant risk and cost. Most patients experience very poor outcomes, although a significant minority respond to or are cured by specific therapies. A 2006 case report describes a child whose treatment-responsive focal epilepsy evolved into treatment-resistant focal epilepsy with an epileptic encephalopathy, illustrating poorly understood age-related changes in drug responsiveness.
A 2021 review of ARX mutations, which cause a spectrum of neurodevelopmental disorders including West syndrome, X-linked infantile spasms, and Ohtahara syndrome, states that these epilepsy phenotypes are often drug resistant and related to intellectual disability. A 2025 systematic review of cannabidiol in children with DEEs included 13 studies with a total of 656 children. Cannabidiol was administered at a maximum dose of 50 mg/kg/day. Almost all studies reported positive outcomes, with a reduction of 50% or above in seizure frequency in at least 20% of patients in 10 studies. Adverse events were common and included somnolence, loss of appetite, diarrhoea, fatigue, and increased serum aminotransferases; most were mild to moderate and reversible. The review concludes that cannabidiol was well tolerated and effectively reduced seizure frequency in children with uncontrolled seizures on concomitant antiepileptic medications.
What is still missing are long-term data on cannabidiol’s effects on development and quality of life, not just seizure counts. The genetic heterogeneity of DEEs means that most patients still lack a precision therapy, and the modest impact of genomic sequencing on treatment decisions points to a gap in translating genetic findings into effective drugs. No randomised controlled trial has yet demonstrated that any agent, including cannabidiol, alters the neurodevelopmental trajectory of DEE 109 specifically.
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.
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.
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.
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.
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.
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.
