DeCure for Developmental and epileptic encephalopathy 108
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy 108 — 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 108 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 108 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
microtubule associated serine/threonine kinase 3 (MAST3) — MAST3 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 3KHF · 1.2 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Developmental and epileptic encephalopathy 108 is one of over 105 genes now linked to the broader category of developmental and epileptic encephalopathies, according to a 2023 reference. These conditions involve developmental impairment driven both by the underlying genetic cause and by frequent epileptic activity. Onset is typically in early childhood. The distinction between developmental encephalopathy, where epileptiform activity has minimal effect on cognition, and epileptic encephalopathy, where cognition can revert toward baseline with treatment, is clinically important but often blurred in practice. For patients with DEE, a precision medicine approach may reduce the overall burden of epilepsy, but the evidence for this remains limited to conceptual frameworks rather than controlled data.
Treatment of most epileptic encephalopathies remains a major challenge. A 2018 review states that most antiseizure drugs are ineffective in these disorders, and the treatments that do work often carry significant risk and cost. Next-generation sequencing has identified many single-gene causes but has had only a modest impact on patient-specific treatment decisions. Most patients experience very poor outcomes, although a significant minority respond to or are cured by specific therapies. No abstract provides response rates, survival data, or sample sizes for any drug in DEE 108 specifically.
A 2020 case report describes a single patient with a de novo CDK19 variant and DEE who had cerebrospinal fluid abnormalities, but no treatment outcome is reported. A 2025 review notes that it is especially important to recognise treatable or modifiable entities within the DEE group, and summarises available precision therapies for well-established syndromes, but does not name any drug or give numerical results for DEE 108. A 2024 review on epileptic encephalopathy lists emerging therapies including gene and stem cell therapy, but again provides no efficacy data.
What is still missing is any clinical trial data, any patient stratification by specific genetic variant, and any funding for studies that would test a repurposed drug in DEE 108. Without a trial designed for this specific genotype, no conclusion about any drug's effect can be drawn.
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.
Neurology Genetics · 2020 · 5 citations · open access
Cerebrospinal fluid abnormalities in developmental and epileptic encephalopathy with a <i>de novo CDK19</i> variant
AbstractDevelopmental and epileptic encephalopathy (DEE) is a spectrum of neurodevelopmental conditions in which psychomotor delay or regression arises in association with frequent epileptic activity. In the past decade, molecular genetics studies showed that DEE is caused by environmental insults and by genetic factors; several de novo pathogenic variants were also identified.1 The authors are indebted to the patient and her parents. The authors would also like to thank Enago ([enago.jp][1]) for the English language review. [1]: http://www.enago.jp/
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 Comprehensive Review on Current Insights Into Epileptic Encephalopathy: Pathogenesis and Therapeutic Strategies
AbstractEpileptic encephalopathy (EE) represents a challenging group of disorders characterized by severe epilepsy and significant cognitive, behavioral, and neurological impairments. This comprehensive review aims to elucidate the current insights into the pathogenesis and therapeutic strategies for these disorders. Pathogenesis involves a complex interplay of genetic factors, neurobiological mechanisms, and environmental influences that contribute to the severity and progression of symptoms. Clinical manifestations are diverse, encompassing various seizure types, cognitive and behavioral impairments, and developmental delays. Current therapeutic strategies include pharmacological treatments, nonpharmacological interventions, and emerging therapies such as gene and stem cell therapy. Despite advancements, significant challenges and limitations remain, highlighting the need for ongoing research and innovation. This review synthesizes existing knowledge, identifies research gaps, and proposes future directions, emphasizing the potential for personalized medicine to improve patient outcomes and quality of life.
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.
