DeCure for Developmental and epileptic encephalopathy, 18
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 18 — screening already-approved drugs against its 3-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, 18 maps to a 3-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, 18 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
telomerase reverse transcriptase (TERT) — TERT 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…
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RCSB Protein Data Bank · entry 9Q16 · 2.7 Å · ligand 2'-deoxy-5'-O-[(R)-hydroxy{[(R)-hydroxy(phosphonooxy)phosphoryl]amino}phosphoryl]guanosine (XG4). Experimental structure, not a prediction.
What the evidence adds up to
In 2016, an in silico prioritisation approach ranked 179 epileptic encephalopathy candidate genes by coexpression with 51 established genes. Five of six subsequently validated candidate genes were among the 19 prioritised in 2013 (odds ratio 54, 95% CI 7 to infinity, p = 4.5 × 10⁻⁵). Nine genes — FBXO41, PLXNA1, ACOT4, PAK6, GABBR2, YWHAG, NBEA, KNDC1, and SELRC1 — were proposed as strong candidates for further investigation. By August 2022, 105 genes were associated with developmental and epileptic encephalopathy (DEE) according to OMIM, and a 2023 study at a reference centre in Northeast Brazil reported that many DEEs have a genetic basis that can alter neurodevelopmental delay independently of epileptiform activity.
A 2024 retrospective study of 21 paediatric patients with epileptic encephalopathy who received pulse intravenous methylprednisolone (IVMP) reported a responder rate (seizure reduction >50%) of 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 effectiveness. All patients showed improvements in quality of life, EEG tracing, and postural-motor development. No relevant adverse events were observed.
A 2025 systematic review of cannabidiol in children with DEEs included 13 studies and 656 children. Cannabidiol was administered at a maximum dose of 50 mg/kg/day. In 10 studies, at least 20% of patients achieved a 50% or greater reduction in seizure frequency. Adverse events were relatively common and included somnolence, loss of appetite, diarrhoea, fatigue, and increased serum aminotransferases; most were mild to moderate and reversible. The review noted that none of the currently available drugs have succeeded in suppressing epileptiform activity in these conditions.
What remains missing are prospective trials that stratify patients by specific genetic aetiologies, long-term outcome data beyond seizure counts — particularly for development and quality of life — and adequately powered studies for rare DEE subtypes such as DEE18. The 2024 IVMP study was small, retrospective, and unblinded. The cannabidiol evidence is drawn from heterogeneous studies with variable designs and no language or date restrictions, and the systematic review did not provide a pooled effect estimate. No study addressed DEE18 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.
Neurology Genetics · 2016 · 22 citations · open access
In silico prioritization based on coexpression can aid epileptic encephalopathy gene discovery
AbstractOBJECTIVE: To evaluate the performance of an in silico prioritization approach that was applied to 179 epileptic encephalopathy candidate genes in 2013 and to expand the application of this approach to the whole genome based on expression data from the Allen Human Brain Atlas. METHODS: PubMed searches determined which of the 179 epileptic encephalopathy candidate genes had been validated. For validated genes, it was noted whether they were 1 of the 19 of 179 candidates prioritized in 2013. The in silico prioritization approach was applied genome-wide; all genes were ranked according to their coexpression strength with a reference set (i.e., 51 established epileptic encephalopathy genes) in both adult and developing human brain expression data sets. Candidate genes ranked in the top 10% for both data sets were cross-referenced with genes previously implicated in the epileptic encephalopathies due to a de novo variant. RESULTS: Five of 6 validated epileptic encephalopathy candidate genes were among the 19 prioritized in 2013 (odds ratio = 54, 95% confidence interval [7,∞], p = 4.5 × 10(-5), Fisher exact test); one gene was false negative. A total of 297 genes ranked in the top 10% for both the adult and developing brain data sets based on coexpression with the reference set. Of these, 9 had been previously implicated in the epileptic encephalopathies (FBXO41, PLXNA1, ACOT4, PAK6, GABBR2, YWHAG, NBEA, KNDC1, and SELRC1). CONCLUSIONS: We conclude that brain gene coexpression data can be used to assist epileptic encephalopathy gene discovery and propose 9 genes as strong epileptic encephalopathy candidates worthy of further investigation.
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.
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.
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.
Russian Journal of Child Neurology · 2024 · 0 citations · open access
Experience of using zonisamide in children in routine clinical practice (a multicenter study)
AbstractBackground. The problem of antiepileptic therapy in children remains highly relevant due to the insufficient efficacy of standard drugs, adverse events, and limitations of clinical guidelines.Aim. To assess the efficacy, tolerability, and continuation of zonisamide (Zonegran) therapy in children with epilepsy.Materials and methods. This retrospective multicenter study was conducted in epileptology centers in various regions of the Russian Federation, including Moscow, Novosibirsk, Krasnodar, Tyumen, Krasnoyarsk, Voronezh, Ryazan). We included 340 patients under the age of 18 (202 boys and 138 girls) with various epileptic syndromes receiving zonisamide (mean age was 10.63 years). Zonisamide was administered to patients with the following epileptic syndromes: age-dependent self-limited focal epilepsy of childhood (n = 49; 14 %) structural focal epilepsy (n = 102; 30 %), focal epilepsy of childhood with structural brain changes and benign epileptiform discharges of childhood visualized at electroencephalography (n = 38; 11.2 %), idiopathic generalized epilepsy (n = 23; 6.7 %), developmental and epileptic encephalopathies (n = 44; 12.9 %) (including developmental and epileptic encephalopathies with spike-and-wave activation during sleep (n = 23; 6.7 %)), Lennox–Gastaut syndrome and infantile epileptic spasms syndrome (n = 32; 9.4 %), genetic epilepsy with generalized and focal seizures (n = 81; 23.8 %). The type of the seizures was distributed as follows: focal motor (n = 205), bilateral tonic-clonic (n = 192), generalized (n = 197), including generalized convulsive (n = 44), tonic (n = 70), atonic (n = 2), myoclonic (n = 26), epileptic spasms (n = 36), absence seizures (n = 19). One patient could have more than one type of seizures. Magnetic resonance imaging demonstrated some changes in 185 patients, whereas 117 patients had no magnetic resonance imaging changes. Thirty-eight patients did not undergo magnetic resonance imaging as they had no indications to it. The most common structural epileptogenic changes were the consequences of perinatal lesions manifesting as cystic-gliotic transformation, atrophy (125 cases in total); less common changes included focal cortical dysplasia, developmental abnormalities (such as polymicrogyria, lissencephaly, holoprosencephaly), mesial temporal sclerosis, and tumors. Zonegran (zonisamide) as an additional therapy was administered at a dose of 3–8 mg/kg/day (mean dose 5 mg/kg/day) to 321 patients.Results. Zonegran (zonisamide) therapy was effective in 257 (75.6 %) of patients; remission was achieved in 174 patients (67.7 %), while reduced seizure frequency (50 % and greater) was registered in 83 patients (32.3 %). A total of 72 patients (21.2 %) reported no adverse events. Twenty participants (5.8 %) had some adverse events; in 4 cases, they were resolved after dosage decrease; in 16 cases, treatment with zonisamide was discontinued.Conclusion. Zonegran (zonisamide) is effective for comprehensive treatment of both focal and generalized epilepsy in children*.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
DRUG RESISTANT EPILEPTIC ENCEPHALOPATHY WITH LATE-ONSET SPASMS
AbstractDevelopmental and epileptic encephalopathy (DEE) is a term used to describe cerebral dysfunction resulting from the underlying cause, epilepsy, or both. There is a subset of DEEs in which there is compelling evidence that the regression is directly tied to the epilepsy itself, where the “epileptic encephalopathy” component of DEE is most evident. Infantile epileptic spasm syndrome (IESS) is perhaps the clearest example.
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.
