DeCure for Developmental and epileptic encephalopathy, 90
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 90 — 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, 90 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, 90 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
fibroblast growth factor 13 (FGF13) — FGF13 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 3HBW · 1.9 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
A 2025 systematic review of 13 studies covering 656 children with developmental and epileptic encephalopathies found that pharmaceutical cannabidiol, at a maximum dose of 50 mg/kg/day, produced a 50% or greater reduction in seizure frequency in at least 20% of patients in 10 of those studies. Adverse events were common: somnolence, loss of appetite, diarrhoea, fatigue, and raised serum aminotransferases, though most were described as mild to moderate and reversible. The review states that none of the currently available drugs have succeeded in suppressing epileptiform activity in these conditions, and that cannabidiol was well tolerated and effectively reduced seizure frequency in children whose seizures were uncontrolled with concomitant antiepileptic medications.
A 2023 study from a reference centre in Northeast Brazil notes that by August 2022 there were 105 genes associated with developmental and epileptic encephalopathy according to OMIM. A 2020 case report describes a patient with a de novo CDK19 variant, but provides no efficacy data for any drug. A 2018 review of de novo variants in epileptic encephalopathies discusses methods for evaluating pathogenic potential of genes, noting that some genes show gain or loss of function, but that several genes warrant further study. A 2013 review states that diagnostic criteria are not well developed and treatment options are very limited, and that clinicians are often unable to diagnose even benign epileptic syndromes. A 2024 comprehensive review lists pharmacological treatments, nonpharmacological interventions, and emerging therapies such as gene and stem cell therapy, but acknowledges significant challenges and limitations remain.
The evidence for cannabidiol is the only quantitative treatment data available in these abstracts, and it shows a modest responder rate — at least 20% of patients achieving a 50% seizure reduction — in a systematic review that included no long-term follow-up. The 2025 review itself calls for future research into long-term effects on seizure control, development, and quality of life. What is still missing are randomised controlled trials that stratify patients by genetic aetiology, long-term safety and developmental outcome data, and any evidence that cannabidiol or any other drug alters the underlying encephalopathy rather than merely reducing seizure frequency. Funding for such trials, particularly for rare genetic subtypes, remains scarce.
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.
Pyridox(am)ine-5-Phosphate Oxidase Deficiency Treatable Cause of Neonatal Epileptic Encephalopathy With Burst Suppression
AbstractPyridox(am)ine-5-phosphate oxidase deficiency is an autosomal recessive disorder of pyridoxine metabolism. Intractable neonatal epileptic encephalopathy is the classical presentation. Pyridoxal-5-phosphate or pyridoxine supplementation improves symptoms. We report a patient with myoclonic and tonic seizures at the age of 1 hour. Pyridoxal-5-phosphate was started on the first day of life and seizures stopped at the age of 3 days, but encephalopathy persisted for 4 weeks. She had normal neurodevelopmental outcome at the age of 12 months on pyridoxal-5-phosphate monotherapy. She had novel homozygous pathogenic frameshift mutation (c.448_451del;p.Pro150Argfs*27) in the PNPO gene. Long-lasting encephalopathy despite well-controlled clinical seizures does neither confirm nor exclude pyridox(am)ine-5-phosphate oxidase deficiency. Normal neurodevelopmental outcome of our patient emphasizes the importance of pyridoxal-5-phosphate treatment. Pyridox(am)ine-5-phosphate oxidase deficiency should be included in the differential diagnosis of Ohtahara syndrome and neonatal myoclonic encephalopathy as a treatable underlying cause. In addition, we reviewed the literature for pyridox(am)ine-5-phosphate oxidase deficiency and summarized herein all confirmed cases.
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/
Journal of Pediatric Neurology · 2020 · 3 citations
Pediatric Metronidazole-Induced Encephalopathy: A Case Report and Review of the Literature
AbstractAbstract Metronidazole-induced encephalopathy is a rare toxic encephalopathy secondary to the common use to this antimicrobial drug. It has been reported mainly in adult patients but only rarely in children. Owing to possible devastating complication of this disease, clinicians should have a higher index of suspicion for encephalopathic patients on metronidazole therapy. Here, we report a 5-month-old infant with metronidazole-induced encephalopathy presenting with nonconvulsive status epilepticus. A review of the literature in pediatric, as well as adult metronidazole-induced encephalopathy, is also provided.
NATIONAL JOURNAL OF NEUROLOGY · 2013 · 0 citations · open access
On the Clinics and Diagnosis of Epileptic Encephalopathy
AbstractEarly childhood is characterized by a continuous process of development of structures and functions of organism, especially central nervous system.The concept of epileptic encephalopathy is based on the assumption that the aggressive epileptic activity during the maturation of the brain is the main causal factor in cognitive and neuropsychological impairment or regress. With age, EEG signs of evolving consistent with the transition into each another. Currently the diagnosis criteria are not well developed and the treatment options are very limited, whereby patients cannot receive adequate treatment that further aggravates encephalopathy. Unfortunately clinicians are often unable to diagnose also benign epileptic syndromes.
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.
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.
