DeCure for Familial focal epilepsy with variable foci
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for familial focal epilepsy with variable foci — screening already-approved drugs against its 8-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFamilial focal epilepsy with variable foci maps to a 8-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 familial focal epilepsy with variable foci 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
NPR2 like, GATOR1 complex subunit (NPRL2) — NPRL2 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 gdpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8FW5 · 3.08 Å · ligand GUANOSINE-5'-DIPHOSPHATE (GDP). Experimental structure, not a prediction.
What the evidence adds up to
Familial focal epilepsy with variable foci (FFEVF) is a rare autosomal dominant focal epilepsy syndrome. As of 2005, the only genes identified for any familial focal epilepsy were those for autosomal-dominant nocturnal frontal lobe epilepsy and familial lateral temporal lobe epilepsy; no specific gene for FFEVF had been confirmed at that time. The 2005 review noted that better phenotype definition allowed identification of distinct syndromes and that genetic counselling and more accurate prognosis were possible for most familial focal epilepsies, but that further linkage studies and candidate gene screening were needed.
A 2020 study of 16 patients with drug-resistant epilepsy (mean age 25 years, range 21–54) who underwent temporal lobe and hippocampal surgery found that 14 (87.5%) had focal cortical dysplasia, 100% had white matter neuronal heterotopia, 100% had neuronal reactive and destructive changes, 100% had epileptic leukoencephalopathy, 12.5% had cortical atrophy, and 2 of 10 examined had hippocampal sclerosis (20%). The authors concluded that the morphopathological heterogeneity in epileptic foci requires an integral approach to pathogenesis and a personalised treatment approach.
A 2023 study of one Chinese family with FFEVF (four patients, one healthy member) identified an NPRL3 c.1137dupT variant. Onset age ranged from 4 months to 31 years. Seizure types were diverse, foci varied (frontal or temporal lobe), seizure timing varied (day or night), and frequency ranged from monthly to daily. Therapeutic effects ranged from refractory epilepsy to almost seizure free. All patients had normal MRI and abnormal EEG (epileptiform discharge, slow wave). Real-time qPCR showed significantly different relative quantities of mRNA between patients and healthy individuals. RT-PCR revealed abnormal splicing in patients compared with the healthy individual. Different family members with the same gene variant had different mRNA splicing, which the authors suggested might cause different phenotypes.
No drug treatment is tested or recommended in any of these abstracts. The 2005 review mentioned that functional studies could lead to new therapeutic strategies, but no such strategies are described. The 2023 study did not report any treatment intervention. What remains missing are large-scale family studies to confirm the range of NPRL3 variants and their effects, functional studies to clarify how abnormal mRNA splicing leads to variable seizure foci, and any clinical trial testing a drug in this specific genetic epilepsy.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Annals of Neurology · 1998 · 120 citations
Familial partial epilepsy with variable foci: A new partial epilepsy syndrome with suggestion of linkage to chromosome 2
AbstractFamilial partial epilepsy with variable foci (FPEVF) joins the recently recognized group of inherited partial epilepsies. We describe an Australian family with 10 individuals with partial seizures over four generations. Detailed electroclinical studies were performed on all affected and 17 clinically unaffected family members. The striking finding was that the clinical features of the seizures and interictal electroencephalographic foci differed among family members and included frontal, temporal, occipital, and centroparietal seizures. Mean age of seizure onset was 13 years (range, 0.75-43 years). Two individuals without seizures had epileptiform abnormalities on electroencephalographic studies. Penetrance of seizures was 62%. A genome-wide search failed to demonstrate definitive linkage, but a suggestion of linkage was found on chromosome 2q with a LOD score of 2.74 at recombination fraction of zero with the marker D2S133. FPEVF differs from the other inherited partial epilepsies where partial seizures in different family members are clinically similar. The inherited nature of this new syndrome may be overlooked because of relatively low penetrance and because of the variability in age at onset and electroclinical features between affected family members.
Genetic Focal Epilepsies: State of the Art and Paths to the Future
AbstractThe concept of genetic focal epilepsies is relatively new as compared to awareness of the importance of genetic factors in the generalized epilepsies. However, in the past decade, there has been increasing recognition of families with dominantly inherited partial epilepsies. Better definition of the phenotypes allows identification of distinct syndromes. The main familial focal epilepsies are autosomal-dominant nocturnal frontal lobe epilepsy (ADNFLE), familial mesial TLE (FMTLE), familial lateral TLE (FLTLE), and familial partial epilepsy with variable foci (FPEVF). The only genes identified so far are those for ADNFLE and FLTLE. In these disorders, functional studies are the next step and could provide advances leading to clarification of the pathophysiology as well as to new therapeutic strategies. At present, we can provide genetic counseling and a more accurate prognosis for most of the familial focal epilepsies. Greater awareness of the genetic basis in this group of disorders by the treating physicians is essential for identification of new families. This will allow further linkage studies, candidate gene screening, and identification of new genes, which will hopefully result in genetically based prevention and treatment.
Russian Journal of Archive of Pathology · 2020 · 5 citations
Structural heterogeneity of epileptic foci in local drug-resistant epilepsy
AbstractBACKGROUND: To study etiopathogenesis is one of the most important tasks of modern neurology. Various types of structural changes occur in drug-resistant epilepsy (DRE); however, they are described as distinct phenomena. OBJECTIVE: To provide a comprehensive characterization of structural changes in the cortex and adjacent white matter in the electrophysiological activity zone (in the epileptic focus) in patients undergoing surgery for DRE. MATERIAL AND METHODS: Biopsy material of fragments of the temporal lobe and hippocampus from 16 patients aged 21 to 54 years (mean age, 25 years) with DRE were intraoperatively obtained at the Prof. A.L. Polenov Russian Research Institute of Neurosurgery. The investigators studied histological sections stained with H&E, toluidine blue according to the Nissl method and the Spielmeyer method, as well as the results of immunohistochemical reactions with glial fibrillary acidic protein (GFAP), vimentin, and neurofilaments (NF) (Dako antibodies, Denmark). RESULTS: Histological examination revealed a set of heterogeneous changes, reflecting the complex pathogenetic interactions that developed during the formation of an epileptic focus. Structural brain damage involved both gray and white matter. Focal cortical dysplasia was diagnosed in 14 (87.5%) cases; white matter neuronal heterotopia in 100%; neuronal reactive and destructive changes in 100%; epileptic leukoencephalopathy (vascular demyelination, microcysts, sclerosis and dystonia, gliosis) in 100%, cortical atrophy in 12.5%, and hippocampal sclerosis in 20% (in 2 out of the 10 examinees). CONCLUSION: The morphopathological heterogeneity in the structure of epileptic foci reflects the complexity of etiopathogenetic interactions, the polymorphism of epileptic manifestations, and the individual nature of formation of the epileptic system, which requires an integral approach to understanding the pathogenesis and morphogenesis of formation of the epileptic system and provides a direction for a personalized approach to epilepsy treatment.
Abstract<div><p>Objective</p><p>Familial focal epilepsy with variable foci (FFEVF) is a rare type of focal epilepsy syndrome; it is associated with <i>NPRL3</i> variant. However, relevant reports are rare in China. We aimed to analyze the clinical features of Chinese patients with FFEVF to understand further the differences between various <i>NPRL3</i> variants and explored the effect of <i>NPRL3</i> variant on mRNA.</p><p>Methods</p><p>We ran a full workup on a family with FFEVF (four patients, one healthy member): an inquiry of medical history, cranial magnetic resonance imaging (MRI), electroencephalogram (EEG), and whole exon sequencing. Their clinical features were compared with those of other FFEVF patients in published reports. The mRNA splicing changes were analyzed quantitatively and qualitatively using real-time quantitative—polymerase chain reaction (q-PCR) and reverse transcription (RT)-PCR and compared between our patients and healthy individuals.</p><p>Results</p><p>Patients with <i>NPRL3</i>: c.1137dupT variant had a wide range of onset age (4 months to 31 years), diverse seizure types, variable foci (frontal lobe/temporal lobe), different seizure times (day/night) and frequencies (monthly/seldom/every day), different therapeutic effects (refractory epilepsy/almost seizure free), normal MRI, and abnormal EEG (epileptiform discharge, slow wave). The phenotypic spectrum with different <i>NPRL3</i> variants was either similar or different. Significantly different relative quantities of mRNA were found between patients and healthy individuals in real-time qPCR. Abnormal splicing was observed in patients compared with healthy individual in RT-PCR. Despite having the same gene variant, different family members had different mRNA splicing, possibly causing different phenotypes.</p><p>Conclusion</p><p>The clinical features of FFEVF varied, and auxiliary inspection was atypical. <i>NPRL3</i>: c.1137dupT could change the relative quantity of mRNA and cause abnormal splicing, which might produce different phenotypes in different family members.</p></div>
Abstract<div><p>Objective</p><p>Familial focal epilepsy with variable foci (FFEVF) is a rare type of focal epilepsy syndrome; it is associated with <i>NPRL3</i> variant. However, relevant reports are rare in China. We aimed to analyze the clinical features of Chinese patients with FFEVF to understand further the differences between various <i>NPRL3</i> variants and explored the effect of <i>NPRL3</i> variant on mRNA.</p><p>Methods</p><p>We ran a full workup on a family with FFEVF (four patients, one healthy member): an inquiry of medical history, cranial magnetic resonance imaging (MRI), electroencephalogram (EEG), and whole exon sequencing. Their clinical features were compared with those of other FFEVF patients in published reports. The mRNA splicing changes were analyzed quantitatively and qualitatively using real-time quantitative—polymerase chain reaction (q-PCR) and reverse transcription (RT)-PCR and compared between our patients and healthy individuals.</p><p>Results</p><p>Patients with <i>NPRL3</i>: c.1137dupT variant had a wide range of onset age (4 months to 31 years), diverse seizure types, variable foci (frontal lobe/temporal lobe), different seizure times (day/night) and frequencies (monthly/seldom/every day), different therapeutic effects (refractory epilepsy/almost seizure free), normal MRI, and abnormal EEG (epileptiform discharge, slow wave). The phenotypic spectrum with different <i>NPRL3</i> variants was either similar or different. Significantly different relative quantities of mRNA were found between patients and healthy individuals in real-time qPCR. Abnormal splicing was observed in patients compared with healthy individual in RT-PCR. Despite having the same gene variant, different family members had different mRNA splicing, possibly causing different phenotypes.</p><p>Conclusion</p><p>The clinical features of FFEVF varied, and auxiliary inspection was atypical. <i>NPRL3</i>: c.1137dupT could change the relative quantity of mRNA and cause abnormal splicing, which might produce different phenotypes in different family members.</p></div>
Abstract<div><p>Objective</p><p>Familial focal epilepsy with variable foci (FFEVF) is a rare type of focal epilepsy syndrome; it is associated with <i>NPRL3</i> variant. However, relevant reports are rare in China. We aimed to analyze the clinical features of Chinese patients with FFEVF to understand further the differences between various <i>NPRL3</i> variants and explored the effect of <i>NPRL3</i> variant on mRNA.</p><p>Methods</p><p>We ran a full workup on a family with FFEVF (four patients, one healthy member): an inquiry of medical history, cranial magnetic resonance imaging (MRI), electroencephalogram (EEG), and whole exon sequencing. Their clinical features were compared with those of other FFEVF patients in published reports. The mRNA splicing changes were analyzed quantitatively and qualitatively using real-time quantitative—polymerase chain reaction (q-PCR) and reverse transcription (RT)-PCR and compared between our patients and healthy individuals.</p><p>Results</p><p>Patients with <i>NPRL3</i>: c.1137dupT variant had a wide range of onset age (4 months to 31 years), diverse seizure types, variable foci (frontal lobe/temporal lobe), different seizure times (day/night) and frequencies (monthly/seldom/every day), different therapeutic effects (refractory epilepsy/almost seizure free), normal MRI, and abnormal EEG (epileptiform discharge, slow wave). The phenotypic spectrum with different <i>NPRL3</i> variants was either similar or different. Significantly different relative quantities of mRNA were found between patients and healthy individuals in real-time qPCR. Abnormal splicing was observed in patients compared with healthy individual in RT-PCR. Despite having the same gene variant, different family members had different mRNA splicing, possibly causing different phenotypes.</p><p>Conclusion</p><p>The clinical features of FFEVF varied, and auxiliary inspection was atypical. <i>NPRL3</i>: c.1137dupT could change the relative quantity of mRNA and cause abnormal splicing, which might produce different phenotypes in different family members.</p></div>
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.
