DeCure for Developmental and epileptic encephalopathy, 42
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 42 — 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, 42 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, 42 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
calcium voltage-gated channel subunit alpha1 A (CACNA1A) — CACNA1A 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 clrdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8X93 · 2.92 Å · ligand CHOLESTEROL (CLR). Experimental structure, not a prediction.
What the evidence adds up to
A 2015 study identified CDKL5 mutations in five Japanese patients (one male, four female) with epileptic encephalopathy; all mutations were de novo and located at positions previously reported as pathogenic, suggesting nucleotide alteration hot spots. A 2023 study from a reference centre in Northeast Brazil notes that by August 2022, 105 genes were associated with developmental and epileptic encephalopathy (DEE) according to OMIM.
A retrospective study from 2020 to 2023 evaluated pulse intravenous methylprednisolone (IVMP) therapy in 21 paediatric patients with epileptic encephalopathy, aged 18 years or younger at treatment and with at least six months of follow-up. The responder rate, defined as seizure reduction greater than 50%, was 85.7% at six and nine months of therapy, and 80.9% at six months after therapy suspension. Genetic aetiology and encephalopathy related to electrical status epilepticus during slow-wave sleep (ESES) were significant predictors of favourable outcome (p = 0.0475). 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, with no relevant adverse events reported. A 2025 review summarises that DEEs are a group of complex paediatric epilepsies with adverse neurodevelopmental outcomes, and that it is important to recognise treatable or modifiable entities within this group.
A 2024 comprehensive review notes that current therapeutic strategies for epileptic encephalopathy include pharmacological treatments, nonpharmacological interventions, and emerging therapies such as gene and stem cell therapy, but states that significant challenges and limitations remain. The same review emphasises the need for ongoing research and innovation, and proposes personalised medicine as a future direction.
What is still missing are prospective, controlled trials with larger sample sizes, standardised outcome measures beyond seizure reduction, and clear stratification by specific genetic aetiology. The retrospective IVMP study is small (21 patients) and uncontrolled, and the predictive value of genetic versus other aetiologies needs replication. No data exist on whether pulse steroid therapy alters long-term developmental trajectory, and the cost and infrastructure for routine IVMP pulse protocols in diverse healthcare settings remain unaddressed.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Genome Variation · 2015 · 8 citations · open access
Recurrent occurrences of CDKL5 mutations in patients with epileptic encephalopathy
AbstractThe cyclin-dependent kinase-like 5 gene (CDKL5) is recognized as one of the genes responsible for epileptic encephalopathy. We identified CDKL5 mutations in five Japanese patients (one male and four female) with epileptic encephalopathy. Although all mutations were of de novo origin, they were located in the same positions as previously reported pathogenic mutations. These recurrent occurrences of de novo mutations in the same loci may indicate hot spots of nucleotide alteration.
Journal of Clinical Medicine · 2024 · 2 citations · open access
Efficacy and Safety of Pulse Intravenous Methylprednisolone in Pediatric Epileptic Encephalopathies: Timing and Networks Consideration
AbstractBackground: Epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early onset, and unfavorable developmental outcomes. This article discusses the use of intravenous methylprednisolone (IVMP) pulse therapy in pediatric patients with EE to evaluate its efficacy and tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction > 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: The study included 21 patients, with a responder rate of 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Variables significantly predicting favorable outcome were etiology (p = 0.0475) and epilepsy type (p = 0.0475), with the best outcome achieved in patients with genetic epilepsy and those with encephalopathy related to electrical status epilepticus during slow-wave sleep (ESES). All patients evidenced improvements in QoL at the last follow-up, with no relevant adverse events reported. Conclusions: Our study confirmed the efficacy and high tolerability of IVMP pulse therapy in pediatric patients with EE. Genetic epilepsy and ESES were positive predictors of a favorable clinical outcome. QOL, EEG tracing, and postural–motor development showed an improving trend as well. IVMP pulse therapy should be considered earlier in patients with EE.
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: ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction >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.
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.
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.
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.
