DeCure for Developmental and epileptic encephalopathy, 27
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 27 — 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, 27 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
approvedKetamineApproved drug
Structures already discussed alongside developmental and epileptic encephalopathy, 27 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
X-ray Structure of the Anesthetic Ketamine — Ketamine has a real, experimentally solved structure in complex with this target (PDB 4F8H, 2.99 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet rkedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4F8H · 2.99 Å · ligand Ketamine (RKE). Experimental structure, not a prediction.
What the evidence adds up to
Developmental and epileptic encephalopathy (DEE) is a group of heterogeneous disorders driven mainly by genetic factors, with onset typically in infancy or early childhood and an overall poor prognosis. PCDH19 is considered one of the most clinically relevant genes in epilepsy, second only to SCN1A, and about 150 mutations have been identified as causative for PCDH19-female epilepsy, also known as early infantile epileptic encephalopathy-9. A de novo CDK19 variant has also been reported in a case of DEE with cerebrospinal fluid abnormalities. The understanding of DEE has evolved from initial genetic underpinnings to a clinically driven term encompassing a broader group of aetiologies, and it is especially important to recognise treatable or modifiable entities within this group.
One retrospective study from 2020 to 2023 examined pulse intravenous methylprednisolone (IVMP) therapy in 21 paediatric patients with epileptic encephalopathy. The responding rate, defined as seizure reduction greater than 50%, was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic aetiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy. The fourth month of therapy was the minimum time point to establish effectiveness. All patients showed improvements in quality of life, EEG tracing, and postural-motor development, and no relevant adverse events were observed.
Current therapeutic strategies for DEE include pharmacological treatments, nonpharmacological interventions, and emerging therapies such as gene and stem cell therapy. Despite these advances, significant challenges and limitations remain. The review literature emphasises that DEEs are individually rare but constitute a sizeable group of paediatric epilepsies, and that precision therapies are available for some well-established syndromes, though the pathogenic mechanisms for many genetic causes, including PCDH19, remain poorly understood.
What is still missing are large, prospective, controlled trials for any single DEE subtype, given the heterogeneity of the disorders. The IVMP study was retrospective and included only 21 patients with mixed aetiologies. Patient stratification by specific genetic mutation, standardised outcome measures beyond seizure reduction, and funding for trials of emerging gene and stem cell therapies are all lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Developmental Neurobiology · 2018 · 45 citations
The Role of Protocadherin 19 (PCDH19) in Neurodevelopment and in the Pathophysiology of Early Infantile Epileptic Encephalopathy‐9 (EIEE9)
AbstractPCDH19 is considered one of the most clinically relevant genes in epilepsy, second only to SCN1A. To date about 150 mutations have been identified as causative for PCDH19-female epilepsy (also known as early infantile epileptic encephalopathy-9, EIEE9), which is characterized by early onset epilepsy, intellectual disabilities, and behavioral disturbances. Although little is known about the physiological role of PCDH19 and the pathogenic mechanisms that lead to EIEE9, in this review, we will present latest researches focused on these aspects, underlining protein expression, its known functions and the mechanisms by which the protein acts, with particular interest in PCDH19 extracellular and intracellular roles in neurons.
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.
Efficacy and Safety of Pulse Intravenous Methylprednisolone in Pediatric Epileptic Encephalopathies: Timing and Networks Consideration
AbstractAbstract: Background: epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early-onset, and unfavorable developmental outcome. We describe a cohort of pediatric patients with EE who underwent intravenous methylprednisolone (IVMP) pulse therapy to examine its efficacy/tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were: &le;18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction &gt;50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of Life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: Twenty-one patients were included. The responding rate was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic etiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy (p=0.0475). The fourth month of therapy was the minimum time point to establish the effectiveness of the treatment. All patients showed improvements in QoL, EEG tracing and postural-motor development. No relevant adverse events were observed. Conclusions: Our study confirms the efficacy and tolerability of pulse IVMP treatment in pediatric patients with EE, especially with genetic etiology and ESES. The fourth month of therapy was the minimum time point to establish its effectiveness. QoL, EEG and postural-motor development also showed improvement.
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.
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.
INDIGO (University of Illinois at Chicago) · 2023 · 0 citations · open access
Table1_Efficacy and safety of ketamine for neonatal refractory status epilepticus: case report and systematic review.docx
AbstractBackground<p>Evidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of neonatal SE and to assess its possible role in the treatment of neonatal SE.</p>Methods<p>We described a novel case and conducted a systematic literature review on neonatal SE treated with ketamine. The search was carried out in Pubmed, Cochrane, Clinical Trial Gov, Scopus and Web of Science.</p>Results<p>Seven published cases of neonatal SE treated with ketamine were identified and analyzed together with our novel case. Seizures typically presented during the first 24 h of life (6/8). Seizures were resistant to a mean of five antiseizure medications. Ketamine, a NMDA receptor antagonist, appeared to be safe and effective in all neonates treated. Neurologic sequelae including hypotonia and spasticity were reported for 4/5 of the surviving children (5/8). 3/5 of them were seizure free at 1–17 months of life.</p>Discussion<p>Neonatal brain is more susceptible to seizures due to a shift towards increased excitation because of a paradoxical excitatory effect of GABA, a greater density of NMDA receptors and higher extracellular concentrations of glutamate. Status epilepticus and neonatal encephalopathy could further enhance these mechanisms, providing a rationale for the use of ketamine in this setting.</p>Conclusions<p>Ketamine in the treatment of neonatal SE showed a promising efficacy and safety profile. However, further in-depth studies and clinical trials on larger populations are needed.</p>
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.
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