DeCure for Developmental and epileptic encephalopathy, 83
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 83 — 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, 83 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, 83 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
NOP2/Sun RNA methyltransferase 6 (NSUN6) — NSUN6 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 sfgdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9IMB · 2.9 Å · ligand SINEFUNGIN (SFG). Experimental structure, not a prediction.
What the evidence adds up to
In a 2023 study from a reference centre in northeast Brazil, the genetic profile of patients with developmental and epileptic encephalopathy was examined. By August 2022, 105 genes were associated with DEE according to OMIM. The disease is defined by developmental impairment related both to the underlying aetiology, independent of epileptiform activity, and to the epileptic encephalopathy itself. Many DEEs have a genetic basis that can by itself alter neurodevelopmental delay.
A 2016 in silico prioritisation study used coexpression data from the Allen Human Brain Atlas to rank genes genome-wide against a reference set of 51 established epileptic encephalopathy genes. Five of six validated candidate genes were among the 19 prioritised in an earlier 2013 list (odds ratio 54, 95% CI 7 to infinity, p = 4.5 × 10⁻⁵). One gene was a false negative. The genome-wide approach identified 297 genes in the top 10% for both adult and developing brain data sets; nine of these had already been implicated in epileptic encephalopathies: FBXO41, PLXNA1, ACOT4, PAK6, GABBR2, YWHAG, NBEA, KNDC1, and SELRC1. A 2018 review of de novo variants in epileptic encephalopathies noted that evaluating pathogenicity requires recurrence in unrelated cases, previously defined phenotypes, and genetic experimental data. Genes showed either gain or loss of function, but several needed further study to confirm their pathogenic potential.
A 2025 systematic review of cannabidiol in children with DEE included 13 studies and 656 children. Cannabidiol was given at a maximum dose of 50 mg/kg/day. Almost all studies reported positive outcomes, with a reduction of 50% or more in seizure frequency in at least 20% of patients in 10 studies. Adverse events were common: somnolence, loss of appetite, diarrhoea, fatigue, and increased serum aminotransferases; most were mild to moderate and reversible. The review concluded that cannabidiol was well tolerated and effectively reduced seizure frequency in children whose seizures were uncontrolled with concomitant antiepileptic medications. A 2023 review of childhood epilepsy noted that many children with pharmacoresistant epilepsy beginning in early infancy progress to DEE, do not achieve remission, and require comprehensive medical care into adulthood.
What is still missing are long-term data on cannabidiol’s effects on development and quality of life, prospective trials that stratify patients by specific genetic aetiologies, and functional validation of the many candidate genes prioritised by coexpression analysis. Funding for such stratified trials and for the experimental studies needed to confirm pathogenicity of the remaining candidate genes is 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.
Genetics in Medicine · 2018 · 61 citations · open access
Evaluating the pathogenic potential of genes with de novo variants in epileptic encephalopathies
AbstractEpileptic encephalopathies comprise a group of catastrophic epilepsies with heterogeneous genetic etiology. Although next-generation sequencing techniques can reveal a number of de novo variants in epileptic encephalopathies, evaluating the pathogenicity of these variants can be challenging. Determining the pathogenic potential of genes in epileptic encephalopathies is critical before evaluating the pathogenicity of variants identified in an individual. We reviewed de novo variants in epileptic encephalopathies, including their genotypes and functional consequences. We then evaluated the pathogenic potential of genes, with the following additional considerations: (1) recurrence of variants in unrelated cases, (2) information of previously defined phenotypes, and (3) data from genetic experimental studies. Genes related to epileptic encephalopathy revealed pathogenicity with distinct functional alterations, i.e., either a gain of function or loss of function in the majority; however, several genes warranted further study to confirm their pathogenic potential. Whether a gene was associated with distinct phenotype, the genotype (or functional alteration)--phenotype correlation, and quantitative correlation between genetic impairment and phenotype severity were suggested to be specific evidence in determining the pathogenic role of genes. Data from epileptic encephalopathy-related genes would be helpful in outlining guidelines for evaluating the pathogenic potential of genes in other genetic disorders.
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.
AbstractChildhood epilepsy is characterized by specific epilepsy syndromes that occur during each developmental age. These "age-dependent" epilepsy syndromes are clinically categorized into a self-limited epilepsy group with good prognosis and high prevalence rate and a pharmacoresistant epilepsy group with poor prognosis despite low prevalence rates. Many children develop pharmacoresistant epilepsy beginning in early infancy and progress to developmental epileptic encephalopathy, which is associated with intellectual, behavioral, and/or motor disabilities. These children do not show remission in epilepsy and are transitioned to the adult service and require comprehensive medical care.
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.
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.
