DeCure for Autosomal dominant nocturnal frontal lobe epilepsy 5
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for autosomal dominant nocturnal frontal lobe epilepsy 5 — 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 moduleAutosomal dominant nocturnal frontal lobe epilepsy 5 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 autosomal dominant nocturnal frontal lobe epilepsy 5 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
sperm associated antigen 1 (SPAG1) — SPAG1 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 adpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 9HB4 · 3.56 Å · ligand ADENOSINE-5'-DIPHOSPHATE (ADP). Experimental structure, not a prediction.
What the evidence adds up to
Autosomal dominant nocturnal frontal lobe epilepsy 5 is one of several genetic partial epilepsies. In a 1995 study of five families from Australia, Britain and Canada containing 47 affected individuals, the disorder was characterised by clusters of brief nocturnal motor seizures with hyperkinetic or tonic manifestations, occurring at a mean of eight attacks per night. Subjects often remained aware throughout attacks. Onset was usually in childhood and persisted through adult life with considerable intra-family variation in severity. Interictal EEG was unhelpful; ictal video-EEG showed partial seizures with frontal lobe semiology. Neuro-imaging was normal. Carbamazepine monotherapy was frequently effective. The disorder showed autosomal dominant inheritance. Seizures were often misdiagnosed as benign nocturnal parasomnias or psychiatric disorders.
A 2000 study of a large three-generation Italian family with eight affected individuals and three obligate carriers mapped a third ADNFLE locus to the pericentromeric region of chromosome 1. Age at onset was around 9 years. Interictal awake and sleep EEG showed no definite epileptiform abnormalities in most patients. Ictal video-EEG again showed partial seizures of frontal lobe origin. Intellectual and neurologic examinations and brain CT or MRI were always normal. Carbamazepine was effective in all treated patients. The known loci on chromosomes 20q13.2 and 15q24 were excluded before genome-wide linkage analysis. The β2 subunit of the nicotinic receptor (CHRNB2) was noted as the most obvious candidate gene within the critical region.
A 1997 review noted that the first genetic defect in an idiopathic epilepsy had been found in autosomal dominant nocturnal frontal lobe epilepsy, described as the archetype of a newly recognised group of inherited partial epilepsies. A 2013 case report highlighted that excessive daytime sleepiness can be the presenting symptom of nocturnal frontal lobe epilepsy, and that the clinical similarity between NFLE nocturnal behaviours and parasomnias, together with poor patient history, makes diagnosis challenging.
What remains missing is a clear understanding of how the identified genetic loci translate into seizure generation in the majority of patients, and whether the effectiveness of carbamazepine observed in these small family studies generalises to larger, genetically heterogeneous populations. No randomised controlled trials have been conducted for this specific genetic subtype. Patient stratification by genotype is not yet standard, and the natural history of the disorder across different mutations remains poorly quantified.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
AbstractThe disorder of autosomal dominant nocturnal frontal lobe epilepsy has recently been identified, and is now delineated in detail. A phenotypically homogeneous group of five families from Australia, Britain and Canada, containing 47 affected individuals, was studied. The largest family contained 25 affected individuals spanning six generations. This disorder is characterized by clusters of brief nocturnal motor seizures, with hyperkinetic or tonic manifestations. Subjects often experienced an aura, and remained aware throughout the attacks. Seizures occurred in clusters (mean eight attacks/night) typically as the individual dozed, or shortly before awakening. The epilepsy usually began in childhood, and persisted through adult life, with considerable intra-family variation in severity. Seizures were often misdiagnosed as benign nocturnal parasomnias, psychiatric and medical disorders. Interictal EEG studies were unhelpful. Ictal video-EEG studies showed that the attacks were partial seizures with frontal lobe seizure semiology. Neuro-imaging was normal. Carbamazepine monotherapy was frequently effective. This disorder showed autosomal dominant inheritance. Recognition of this entity is clinically important for diagnosis, appropriate therapy and genetic counselling. Moreover, this disorder now offers an opportunity to identify a gene for partial epilepsy.
A new locus for autosomal dominant nocturnal frontal lobe epilepsy maps to chromosome 1
AbstractBACKGROUND: Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is caused by mutations in the alpha4 subunit of the neuronal nicotinic acetylcholine receptor (CHRNA4) gene, mapping on chromosome 20q13.2. A second ADNFLE locus was mapped on chromosome 15q24. OBJECTIVE: To report a new third ADNFLE locus on chromosome 1 in a large Italian family. METHODS: The authors performed a clinical and genetic study in a large, three-generation ADNFLE family from southern Italy, including eight affected individuals and three obligate carriers. RESULTS: The age at onset of seizures was around 9 years of age and all affected individuals manifested nocturnal partial seizures of frontal lobe origin. Interictal awake and sleep EEG recordings showed no definite epileptiform abnormalities in most patients. Ictal video-EEG showed that the attacks were partial seizures with a frontal lobe semiology. Intellectual and neurologic examinations, and brain CT or MRI results were always normal. Carbamazepine was effective in all treated patients. Exclusion mapping of the known loci linked to ADNFLE-ENFL1, and ENFL2, on chromosomes 20q13.2 and 15q24-was performed on the pedigree before starting the genome-wide linkage analysis. The whole genome scan mapping allowed the identification of a new ADNFLE locus spanning the pericentromeric region of chromosome 1. CONCLUSIONS: The authors provided evidence for a third locus associated to autosomal dominant nocturnal frontal lobe epilepsy on chromosome 1. Among the known genes mapping within this critical region, the ss2 subunit of the nicotinic receptor (CHRNB2) represents the most obvious candidate.
Current Opinion in Neurology · 1997 · 37 citations
Genetics of human partial epilepsy
AbstractA minor genetic predisposition to partial epilepsy has been long recognized. Recently, a group of idiopathic partial epilepsies with autosomal dominant inheritance has been identified. The clinical features and molecular genetic findings in these epilepsies are outlined in the present review. The first genetic defect in an idiopathic epilepsy has been found in autosomal dominant nocturnal frontal lobe epilepsy, the archetype of this newly recognized group of inherited partial epilepsies.
AbstractSummary Autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is characterized by clusters of brief motor seizures. This rare syndrome is caused by mutations in at least two subunit genes of the neuronal nicotinic acetylcholine receptor (nAChR). Some of these mutations seem to increase the risk for additional neurologic symptoms. For an expanded treatment of this topic see Jasper’s Basic Mechanisms of the Epilepsies, Fourth Edition (Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado‐Escueta AV, eds) published by Oxford University Press (available on the National Library of Medicine Bookshelf [NCBI] at http://www.ncbi.nlm.nih.gov/books ).
Epileptic Disorders · 2010 · 12 citations · open access
Malignant autosomal dominant frontal lobe epilepsy with repeated episodes of status epilepticus: successful treatment with vagal nerve stimulation
AbstractAutosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) is a familial partial epilepsy syndrome characterized by seizures suggesting a frontal lobe origin occurring predominantly during sleep. Up to a third of patients may have refractory seizures, with repeated episodes of status epilepticus, intellectual disability of variable degree and psychiatric disturbances. We report a patient with ADNFLE, refractory seizures and repeated episodes of life-threatening convulsive status epilepticus who underwent prolonged video-EEG monitoring and was implanted with a vagal nerve stimulator. At 3.5 years of follow-up, a decrease of more than 80% in seizure frequency was achieved, episodes of status were completely controlled and he displayed improved mood and alertness. Vagal nerve stimulation may be considered as therapy for patients with refractory epilepsies of genetic cause, as well as repeated status epilepticus.
Journal of Family Medicine and Primary Care · 2013 · 2 citations · open access
Nocturnal frontal lobe epilepsy presenting as excessive daytime sleepiness
AbstractExcessive daytime sleepiness (EDS) is common in the general population. Etiologies include insufficient sleep and primary sleep disorders. Due to its high prevalence, physicians often overlook EDS as a significant problem. However, EDS may also be the presenting symptom of seizures, in particular Nocturnal Frontal Lobe Epilepsy (NFLE). Due to the clinical similarity between the nocturnal behaviors of NFLE and parasomnias, and poor patient-related history, NFLE remains a challenging diagnosis. We report the case of a patient with NFLE who presented with a primary complaint of EDS, and discuss the differential diagnosis and evaluation of patients with EDS associated with nocturnal behaviors. In the context of a patient presenting with EDS and stereotyped nocturnal events, clinical suspicion should be high for NFLE.
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.
