DeCure for Developmental and epileptic encephalopathy, 87
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy, 87 — 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, 87 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, 87 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.
What the evidence adds up to
A 2015 review of epileptic encephalopathy notes that cognitive and developmental outcomes are thought to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent seizures and epileptiform discharges, but it presents only critical questions and steps that may help improve outcomes, not data from a trial. A 2015 diagnostic study of over 800 patients with epileptic encephalopathy describes a comprehensive NGS-based panel developed to identify molecular defects, aiming to improve diagnosis and introduce specific treatment options, but it reports no treatment outcomes.
A 2016 in silico prioritisation study tested whether coexpression data could aid gene discovery. Of 179 candidate genes, 6 had been validated by the time of analysis; 5 of those 6 were among 19 prioritised in 2013 (odds ratio 54, 95% CI 7 to infinity, p = 4.5 × 10⁻⁵). One validated gene was a false negative. Genome-wide ranking identified 297 genes in the top 10% for coexpression with a reference set of 51 established epileptic encephalopathy genes in both adult and developing brain data. Nine of those 297 had been previously implicated: FBXO41, PLXNA1, ACOT4, PAK6, GABBR2, YWHAG, NBEA, KNDC1, and SELRC1. The authors propose these nine as strong candidates for further investigation.
A 2019 case report describes an 8-month-old girl with EIEE 65 caused by a de novo CYFIP2 mutation (c.260G>T, p.Arg87Leu). After resistance to levetiracetam, phenobarbital, VitB6, topiramate, methylprednisolone, prednisone, and valproic acid over two months, she became seizure-free several days after vigabatrin was started, and her developmental delay steadily improved. The authors state this is the first demonstration that vigabatrin might be effective for seizure control and improved outcomes in these patients, but this is a single case. A 2020 report on a de novo CDK19 variant in DEE describes no treatment or outcome data, only acknowledging the patient and her parents.
What is missing: no randomised trial or controlled cohort exists for any drug in this specific DEE87 population. The vigabatrin evidence is a single case. The genetic candidates from the 2016 study remain unvalidated by functional or clinical work. No trial funding, no prospective design, and no patient stratification strategy have been reported for this indication.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Epilepsia · 2015 · 29 citations · open access
Epileptic encephalopathies: Optimizing seizure control and developmental outcome
AbstractCognitive and developmental outcomes in patients with epileptic encephalopathy are hypothesized to result from an interplay between the underlying epileptic pathologic substrate and the acquired consequences of frequent and repetitive seizures and epileptiform discharges that often straddle the interictal and ictal boundaries. This article briefly reviews the evidence related to this assumption, presents critical questions that need to be answered to clarify this relationship, and advances a set of concrete steps that may help improve developmental patient outcomes.
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.
Early diagnosis improving the outcome of an infant with epileptic encephalopathy with cytoplasmic FMRP interacting protein 2 mutation
AbstractRATIONALE: Early infantile epileptic encephalopathy (EIEE) 65 was recently shown to be caused by the cytoplasmic FMRP interacting protein 2 (CYFIP2) mutation. To date, only 5 cases have been reported in two articles, and all the outcomes in all cases were poor. PATIENT CONCERNS: In this study, we reported an 8-month-old girl with a 1 month-long history of seizures and developmental delay. Over 1 month later, she developed epileptic spasms in clusters with hypsarrhythmia on electroencephalography. DIAGNOSIS: The patient was diagnosed with EIEE 65 and trio-based whole-exome sequencing revealed a causative de novo CYFIP2 mutation c.260G >T (p.Arg87Leu). INTERVENTIONS: The proband was successively treated with multiple antiepileptic drugs, including levetiracetam, phenobarbital, VitB6, topiramate, methylprednisolone, prednisone, valproic acid and vigabatrin. OUTCOMES: After resistance to multiple anti-epileptic drugs over 2 months of treatment, she finally achieved seizure-free several days after vigabatrin administration and her developmental delay steadily improved. LESSONS: OUR: case confirmed that CYFIP2 was the pathogenic gene of EIEE 65. We also first demonstrated vigabatrin might be effective for control of seizures and helpful for the improved outcomes of these patients.
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/
Comprehensive NGS-Based Diagnostics in over 800 Patients with Epileptic Encephalopathy
AbstractAims: Epileptic encephalopathy (EE) is a severe form of epilepsy with additional psychomotor retardation. EEs have a very heterogeneous background with overlapping phenotypes. Identifying the underlying molecular defect can be very important to improve diagnosis, introduce specific or novel treatment options, and to estimate recurrence risks. For this purpose, we have developed a comprehensive diagnostic panel for epileptic encephalopathy, which is frequently updated.
IAR Journal of Medical Case Reports · 2022 · 0 citations · open access
GABRB3 Gene Mutation with Early Infantile Epileptic Encephalopathy with Co-existent Biotinidase and G6PD Deficiency.
AbstractGABRB3 gene mutations are known to cause early infantile epileptic encephalopathy (EIEE). We report a male infant who presented at 2 months of age with feeding difficulties, intractable seizures and developmental regression. Genetic testing revealed a likely pathogenic GABRB3 (c.860C>T; p.Thr287Ile) mutation along with biotinidase deficiency and G6PD deficiency. Despite multiple antiepileptic drugs, seizures remained frequent until biotin supplementation was started, after which seizure frequency decreased and skin/hair changes improved. This case highlights the importance of genetic and metabolic evaluation in infants with early-onset refractory epilepsy.
NATIONAL JOURNAL OF NEUROLOGY · 2023 · 0 citations · open access
CLINICAL AND PARACLINICAL CHARACTERISTICS OF EPILEPTIC ENCEPHALOPATHY IN EARLY CHILDHOOD
AbstractIn this article, based on the psychoneurological and clinical-paraclinical study of 72 children with epileptic encephalopathy under 3 years of age, a complete analysis of the clinical syndromes of the disease was conducted. Most researchers consider this disease to be a form of interictal epileptic psychosis. Therefore, determining the specificity of the course of this disease helps to make an early diagnosis of this process and make a differential diagnosis from other diseases.
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.
