DeCure for Developmental and epileptic encephalopathy 96
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for developmental and epileptic encephalopathy 96 — 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 96 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 96 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
Developmental and epileptic encephalopathy 96 is one of a group of heterogeneous disorders characterised by drug-resistant seizures and neurodevelopmental delay, with onset typically in infancy or early childhood and an overall poor prognosis. The condition is mainly driven by genetic factors. No specific drug treatment for DEE96 is mentioned in the reviewed abstracts.
A 2016 study used an in silico prioritisation approach based on brain gene coexpression data to rank candidate genes for epileptic encephalopathy. Of 179 candidate genes evaluated in 2013, 19 were prioritised; five of six subsequently validated genes were among those 19, yielding an odds ratio of 54 (95% confidence interval 7 to infinity, p = 4.5 × 10⁻⁵). One validated gene was a false negative. Applying the same method genome-wide, 297 genes ranked in the top 10% for coexpression with a reference set of 51 established epileptic encephalopathy genes in both adult and developing human brain data. Nine of those 297 had already been implicated in epileptic encephalopathies: FBXO41, PLXNA1, ACOT4, PAK6, GABBR2, YWHAG, NBEA, KNDC1, and SELRC1. None of these nine is DEE96.
A 2018 review of de novo variants in epileptic encephalopathies noted that evaluating pathogenicity requires evidence such as recurrence in unrelated cases, previously defined phenotypes, and data from genetic experimental studies. Genes showed distinct functional alterations, either gain or loss of function, but several required further study to confirm their pathogenic potential. The 2024 review on developmental and epileptic encephalopathy restates the definition and genetic aetiology but provides no new trial data, no survival or response rates, and no drug-specific results.
What is still missing is any clinical trial testing a drug for DEE96 specifically, any patient stratification by genotype, and any funding directed at this particular subtype. The genetic basis is recognised, but no precision treatment has been reported.
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.
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.
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.
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.
