DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for seizures, benign familial infantile, 3 — 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 moduleSeizures, benign familial infantile, 3 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 seizures, benign familial infantile, 3 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
sodium voltage-gated channel alpha subunit 2 (SCN2A) — SCN2A 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 3beta,14beta,17beta,25rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6J8E · 3.0 Å · ligand (3beta,14beta,17beta,25R)-3-[4-methoxy-3-(methoxymethyl)butoxy]spirost-5-en (9Z9). Experimental structure, not a prediction.
What the evidence adds up to
In a cohort of 36 families with familial neonatal seizures, 33 met clinical criteria for benign familial neonatal epilepsy (BFNE). Of those, 27 families had KCNQ2 mutations, one had a KCNQ3 mutation, and two had SCN2A mutations. Seizures persisting after age 6 months occurred in 31% of individuals with KCNQ2 mutations, and later seizures were associated with frequent neonatal seizures. Two mutation-negative BFNE families had linkage to known loci excluded, suggesting a further gene is involved. The three families that did not meet BFNE criteria due to developmental delay or intellectual disability had a molecular lesion identified in two; the other remained unsolved. The molecular cause was identified in 91% of the families overall.
A separate pedigree with three affected individuals over three generations showed onset of focal seizures between 4 and 12 months, with good response to antiepileptic drugs and no later epilepsy. A novel heterozygous SCN2A mutation c.3003 T>A was found. The authors note that benign familial infantile seizures (BFIS) and benign familial neonatal-infantile seizures (BFNIS) may share the same genetic abnormality. An earlier review of 15 families with 116 affected individuals reported onset by 2 to 8 days of life, cessation by 1 to 6 months, normal neurodevelopmental outcome, and an 11% rate of subsequent seizures in childhood or adulthood. Another report describes an autosomal dominant neonatal-infantile seizure disorder with a 20% empiric risk of subsequent epilepsy in one form and no increased risk in another.
A 2021 overview lists KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A, and SCN8A as genes implicated in neonatal epilepsies, including benign familial neonatal epilepsy, early myoclonic encephalopathy, and Ohtahara syndrome. The 2023 ILAE Genetic Literacy Series describes self-limited familial epilepsies with neonatal or infantile onset as autosomal dominant disorders with focal motor seizures that remit during infancy or early childhood, noting incomplete penetrance and de novo inheritance. What remains missing is prospective data on how often unsolved families harbour novel genes, systematic stratification by seizure frequency in the neonatal period to predict later epilepsy risk, and funding for long-term follow-up studies that could clarify whether the 11–31% rate of later seizures is modifiable by early treatment.
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 · 128 citations
Familial neonatal seizures in 36 families: Clinical and genetic features correlate with outcome
AbstractOBJECTIVE: We evaluated seizure outcome in a large cohort of familial neonatal seizures (FNS), and examined phenotypic overlap with different molecular lesions. METHODS: Detailed clinical data were collected from 36 families comprising two or more individuals with neonatal seizures. The seizure course and occurrence of seizures later in life were analyzed. Families were screened for KCNQ2, KCNQ3, SCN2A, and PRRT2 mutations, and linkage studies were performed in mutation-negative families to exclude known loci. RESULTS: Thirty-three families fulfilled clinical criteria for benign familial neonatal epilepsy (BFNE); 27 of these families had KCNQ2 mutations, one had a KCNQ3 mutation, and two had SCN2A mutations. Seizures persisting after age 6 months were reported in 31% of individuals with KCNQ2 mutations; later seizures were associated with frequent neonatal seizures. Linkage mapping in two mutation-negative BFNE families excluded linkage to KCNQ2, KCNQ3, and SCN2A, but linkage to KCNQ2 could not be excluded in the third mutation-negative BFNE family. The three remaining families did not fulfill criteria of BFNE due to developmental delay or intellectual disability; a molecular lesion was identified in two; the other family remains unsolved. SIGNIFICANCE: Most families in our cohort of familial neonatal seizures fulfill criteria for BFNE; the molecular cause was identified in 91%. Most had KCNQ2 mutations, but two families had SCN2A mutations, which are normally associated with a mixed picture of neonatal and infantile onset seizures. Seizures later in life are more common in BFNE than previously reported and are associated with a greater number of seizures in the neonatal period. Linkage studies in two families excluded known loci, suggesting a further gene is involved in BFNE.
A Novel <i>SCN2A</i> Mutation in Family with Benign Familial Infantile Seizures
AbstractBenign familial infantile seizures (BFIS) is a clinical entity characterized by focal seizures with or without secondary generalization, occurring mostly in clusters, and usually first seen between 4 and 8 months of life. Psychomotor development is normal, and seizures usually resolve within the first year of life. BFIS is a genetically heterogenous condition with loci mapped to chromosomes 19 and 16. Mutations in the voltage-gated sodium channel alpha2 subunit (SCN2A) gene on chromosome 2 were recently identified in families affected by neonatal and infantile seizures (benign familial neonatal-infantile seizures, BFNIS) with typical onset before 4 months of life. The identification of SCN2A mutations in families with only infantile seizures indicated that BFNIS and BFIS show overlapping clinical features. We report a pedigree showing three affected individuals over three generations. All subjects experienced clusters of focal seizures with or without secondary generalization and onset between 4 and 12 months of life. Response to antiepileptic drugs and the outcome were good. No subjects had other forms of epilepsy later in the life. Neonatal or febrile seizures did not occur in the family. Genetic study in this family revealed a novel heterozygous mutation c.3003 T>A in the SCN2A gene. Comparative analysis of different sodium channel alpha subunits indicates that the mutated residue is highly conserved throughout the evolution, suggesting an important functional role for this domain. Additional families with the infantile form of benign familial seizures should be investigated to corroborate that BFIS and BFNIS may share the same genetic abnormality.
American Journal of Medical Genetics · 1983 · 64 citations
Benign familial neonatal‐infantile seizures
AbstractWe report on an autosomal dominant neonatal-infantile seizure disorder and offer criteria for establishing the diagnosis and guidelines for the evaluation and treatment of this disorder. Long-term anticonvulsant treatment usually is not required. The subsequent risk of a recurrent seizure disorder depends on whether other affected relatives developed a seizure disorder later in life. This disorder may have at least two different neonatally indistinguishable forms: one having an increased empiric risk (20%) of subsequent epilepsy, and a second which carries no increased risk. These familial neonatal-infantile seizures are termed "benign" since they are not associated with subsequent psychomotor retardation.
Brain Sciences · 2021 · 38 citations · open access
Neonatal Seizures: An Overview of Genetic Causes and Treatment Options
AbstractSeizures are the most frequent neurological clinical symptoms of the central nervous system (CNS) during the neonatal period. Neonatal seizures may be ascribed to an acute event or symptomatic conditions determined by genetic, metabolic or structural causes, outlining the so-called ‘Neonatal Epilepsies’. To date, three main groups of neonatal epilepsies are recognised during the neonatal period: benign familial neonatal epilepsy (BFNE), early myoclonic encephalopathy (EME) and ‘Ohtahara syndrome’ (OS). Recent advances showed the role of several genes in the pathogenesis of these conditions, such as KCNQ2, KCNQ3, ARX, STXBP1, SLC25A22, CDKL5, KCNT1, SCN2A and SCN8A. Herein, we reviewed the current knowledge regarding the pathogenic variants most frequently associated with neonatal seizures, which should be considered when approaching newborns affected by these disorders. In addition, we considered the new possible therapeutic strategies reported in these conditions.
American Journal of Medical Genetics · 1984 · 36 citations
Familial neonatal and infantile seizures: An autosomal‐dominant disorder
AbstractFamilial neonatal seizures are an important and probably underrecognized disorder. A family with six affected individuals in three generations was evaluated and their clinical characteristics were compared with those of 15 families previously reported in the literature. An analysis of the 116 affected individuals uncovered a typical clinical picture of onset of seizures by 2 to 8 days of life in an otherwise healthy appearing infant, and cessation of seizures by 1 to 6 months. Results of diagnostic evaluations were normal, and the pathogenesis of the disorder is still unclear. Long-term neurodevelopmental outcome was normal except for an increased rate (11%) of subsequent seizures in childhood or as an adult. The disorder was inherited as an autosomal-dominant trait with a high degree of penetrance.
Epileptic Disorders · 2023 · 21 citations · open access
ILAE Genetic Literacy Series: Self‐limited familial epilepsy syndromes with onset in neonatal age and infancy
AbstractThe self-limited (familial) epilepsies with onset in neonates or infants, formerly called benign familial neonatal and/or infantile epilepsies, are autosomal dominant disorders characterized by neonatal- or infantile-onset focal motor seizures and the absence of neurodevelopmental complications. Seizures tend to remit during infancy or early childhood and are therefore called "self-limited". A positive family history for epilepsy usually suggests the genetic etiology, but incomplete penetrance and de novo inheritance occur. Here, we review the phenotypic spectrum and the genetic architecture of self-limited (familial) epilepsies with onset in neonates or infants. Using an illustrative case study, we describe important clues in recognition of these syndromes, diagnostic steps including genetic testing, management, and genetic counseling.
SAGE Open Medical Case Reports · 2024 · 0 citations · open access
Three siblings with self-limited familial infantile epilepsy with <i>PRRT2</i> mutation: A case series
AbstractWe report three sisters with self-limited familial infantile epilepsy, caused by a mutation in proline-rich transmembrane protein2. Self-limited familial infantile epilepsy has been established as a distinct epileptic syndrome characterized by focal seizures in clusters of infantile-onset. The seizure types of our cases were focal with or without secondary generalization. The seizures manifested at 3-5 months of age, and each lasted 1-2 min. All three sisters fulfilled the criteria for self-limited familial infantile epilepsy, except in one case who showed interictal spikes in the right central area. The seizures were controlled with carbamazepine. When carbamazepine treatment was started, one case developed a rash, and her treatment was switched to valproic acid. However, the seizures persisted in this case such that carbamazepine was restarted. The rash did not recur. Electroencephalography showed spikes in only one case on interictal electroencephalography. All three sisters were developmentally normal, and no dyskinesia was observed during follow-up. All three sisters and their father, but not their mother, had the following pathogenic variant in proline-rich transmembrane protein2: NM_001256442.2(PRRT2): c.649dup[p.(Arg217Profs*8)]. This mutation has been identified in the majority of families with self-limited familial infantile epilepsy, paroxysmal kinesigenic dyskinesia, and/or infantile convulsion and choreoathetosis. Their father had no history of either self-limited familial infantile epilepsy or paroxysmal kinesigenic dyskinesia. The lack of a clear genotype-phenotype correlation was demonstrated in our cases with this proline-rich transmembrane protein2 mutation.
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.
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