DeCure for Generalized epilepsy with febrile seizures plus, type 7
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for generalized epilepsy with febrile seizures plus, type 7 — 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 moduleGeneralized epilepsy with febrile seizures plus, type 7 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
approvedLamotrigineApproved drug
Structures already discussed alongside generalized epilepsy with febrile seizures plus, type 7 in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Cryo-EM structure of Nav1.7 — Lamotrigine has a real, experimentally solved structure in complex with this target (PDB 8THH, 2.7 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet iyjdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8THH · 2.7 Å · ligand Lamotrigine (IYJ). Experimental structure, not a prediction.
What the evidence adds up to
Generalised epilepsy with febrile seizures plus, type 7 is not named in any of the provided abstracts. The abstracts discuss febrile seizures in general and idiopathic generalised epilepsy syndromes as a broad category. In a cohort of 890 patients with newly diagnosed epilepsy, 118 (13%) met criteria for idiopathic generalised epilepsy syndromes; 66 of 103 with known outcomes (64%) achieved remission. A history of febrile seizures was the only factor associated with reduced likelihood of remission (p = 0.032). Among patients with febrile seizures, 247 of 345 (71.6%) had simple febrile seizures, 89 (25.8%) had complex febrile seizures, and 9 (2.6%) had febrile status epilepticus. After one year of follow-up, only 4 patients (1.15%), all with complex febrile seizures, were diagnosed with epilepsy.
Treatment data from the 2019 study show that 195 patients with febrile seizures were followed without treatment; among those treated, 48.6% received rectal diazepam, 23.3% sodium valproate, 23.3% levetiracetam, and 4.6% phenobarbital. The 2000 review states that daily prophylaxis with antiepileptic agents should never be used routinely in simple febrile seizures, only in highly selected cases if at all. Intermittent diazepam prophylaxis at times of fever may or may not reduce recurrence rate but does not appear to improve long-term outcome compared with short-term seizure control. The 2009 recommendations similarly note that both continuous and intermittent anticonvulsant therapy are efficacious in preventing single febrile seizures, but side effects may outweigh benefits, and treatment is indicated only in very selected patients.
The 2012 review on antiepileptogenesis targets states that current anticonvulsant medications appear to influence only the acute process of ictogenesis, not the underlying epileptogenic process. It notes that pathogenic mechanisms producing epilepsy after prolonged febrile convulsions are poorly understood, and that there is unlikely to be one fundamental pathophysiologic mechanism shared by all epilepsies. The 2007 study found that sodium valproate had a superior responder rate (66% vs 45%, p = 0.073) compared with lamotrigine, particularly in juvenile myoclonic epilepsies (75% vs 39%, p = 0.014), but this comparison is for idiopathic generalised epilepsy syndromes, not specifically for generalised epilepsy with febrile seizures plus, type 7.
What is missing: no abstract addresses generalised epilepsy with febrile seizures plus, type 7 specifically; there are no genetic or biomarker data for this subtype; no trial has tested any drug in a cohort defined by this genetic diagnosis; patient stratification by the underlying SCN1A or other mutation is absent from all studies cited; funding for a dedicated prospective trial in this rare syndrome has not 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.
Epilepsia · 2009 · 171 citations
Recommendations for the management of “febrile seizures” Ad hoc Task Force of LICE Guidelines Commission
AbstractFebrile seizures are the most common seizure disorder in childhood, affecting 2-5% of children. Simple febrile seizure is defined as a short (<15 min) generalized seizure, not recurring within 24 h, that occurs during a febrile illness not resulting from an acute disease of the nervous system in a child aged between 6 months and 5 years, with no neurologic deficits and no previous afebrile seizures. These recommendations address the instructions for management of the first febrile seizures, giving criteria for hospital admission, diagnosis, differential diagnosis, and treatment of a prolonged seizure. The authors stressed the benign prognosis of the majority of cases and the risk factors for recurrence of febrile seizures and appearance of epilepsy later on. Both continuous and intermittent anticonvulsant therapy are efficacious in preventing single febrile seizures, but side effects may be so important to overcome the benefits. These treatments are indicated in very selected patients.
AbstractRecent epidemiologic data indicate that the vast majority of children with febrile seizures have a normal longterm outcome. A precise knowledge of the short- and long-term outcome with or without treatment, and short- and long-term side effects is an important prerequisite for assessing the various treatment strategies. We focus on the impact of short-term or prophylactic treatment on the short- and long-term outcome of various types of febrile seizures. There is universal agreement that daily prophylaxis with antiepileptic agents should never be used routinely in simple febrile seizures, but only in highly selected cases, if at all. Intermittent diazepam (DZP) prophylaxis at times of fever may or may not reduce the recurrence rate, but it does not appear to improve the long-term outcome as compared with short-term seizure control. The treatment may be used to reduce the recurrence rate for a small arbitrarily defined group with multiple simple febrile seizures, complex febrile seizures, especially focal, prolonged or both, febrile status, and when parental anxiety is severe. However, there is no evidence that treatment of simple febrile seizures can prevent the rare cases of later epilepsy, and many children with complex febrile seizures have a benign long-term outcome, even without treatment. Many prefer a "wait and see" policy. An attractive alternative is to treat new febrile seizures with rectal DZP in solution at seizure onset, given by the parents at home to prevent febrile status. Newer, less well documented short-term strategies include nasal, oral, or rectal administration of other benzodiazepines. Short-term seizure control of febrile status and careful parental counseling are the two most important targets of treatment.
Finding a better drug for epilepsy: Antiepileptogenesis targets
AbstractFor several decades, both in vitro and in vivo models of seizures and epilepsy have been employed to unravel the molecular and cellular mechanisms underlying the occurrence of spontaneous recurrent seizures (SRS)-the defining hallmark of the epileptic brain. However, despite great advances in our understanding of seizure genesis, investigators have yet to develop reliable biomarkers and surrogate markers of the epileptogenic process. Sadly, the pathogenic mechanisms that produce the epileptic condition, especially after precipitating events such as head trauma, inflammation, or prolonged febrile convulsions, are poorly understood. A major challenge has been the inherent complexity and heterogeneity of known epileptic syndromes and the differential genetic susceptibilities exhibited by patients at risk. Therefore, it is unlikely that there is only one fundamental pathophysiologic mechanism shared by all the epilepsies. Identification of antiepileptogenesis targets has been an overarching goal over the last decade, as current anticonvulsant medications appear to influence only the acute process of ictogenesis. Clearly, there is an urgent need to develop novel therapeutic interventions that are disease modifying-therapies that either completely or partially prevent the emergence of SRS. An important secondary goal is to develop new treatments that can also lessen the burden of epilepsy comorbidities (e.g., cognitive impairment, mood disorders) by preventing or reducing the deleterious changes during the epileptogenic process. This review summarizes novel antiepileptogenesis targets that were critically discussed at the XIth Workshop on the Neurobiology of Epilepsy (WONOEP XI) meeting in Grottaferrata, Italy. Further, emerging neurometabolic links among several target mechanisms and highlights of the panel discussion are presented.
Outcomes of newly diagnosed idiopathic generalized epilepsy syndromes in a non-pediatric setting
AbstractINTRODUCTION: The prognosis of idiopathic generalized epilepsy syndromes (IGES) in the adult setting may vary from that in children owing to differences in genetic, environmental and lifestyle factors. METHODS: All patients diagnosed with epilepsy at the Epilepsy Unit, Western Infirmary, Glasgow, between 1981 and 2001 were reviewed. RESULTS: Of 890 patients, 118 (13%) met the criteria for IGES. Outcomes were known for 103, 66 (64%) of whom achieved remission. The responder rate with sodium valproate was superior (66% vs 45%, P = 0.073) to that with lamotrigine (LTG) particularly in patients with juvenile myoclonic epilepsies (75% vs 39%, P = 0.014). History of febrile seizures was the only factor associated with reduced likelihood of remission (P = 0.032) CONCLUSIONS: Idiopathic generalized epilepsy syndromes constituted 13% of cases in a largely adult cohort of newly diagnosed epilepsy, most of whom achieved remission usually with a single antiepileptic drug. History of febrile seizures was associated with a poorer outcome.
SiSli Etfal Hastanesi Tip Bulteni / The Medical Bulletin of Sisli Hospital · 2019 · 14 citations · open access
Clinical Features and Evaluation in Terms of Prophylaxis of Patients with Febrile Seizures
AbstractOBJECTIVES: Febrile seizures are the most common seizure type of childhood, and prognosis is usually good. Many factors that increase the risk of recurrence and develop epilepsy have been identified. This study aims to determine the clinical characteristics of patients who were admitted with the febrile seizure, and determine the outcomes of the treatment, and the risk factors. METHODS: Between January 2017 and January 2019, 147 (42.6%) female and 198 (57.4%) male patients who were admitted with febrile seizure, and aged between 3-60 months were included in the study. RESULTS: The mean age at the time of admission was 30.4±15.4 months, and the mean age of the first seizure was 21.2±12.8 months. Simple febrile seizure was seen in 247 (71.6%) patients, and complex febrile seizure was seen in 89 (25.8%) patients while febrile status epilepticus was present in 9 (2.6%) patients. Amongst the patients, 59.1% of them had a history of repetitive febrile seizure. First-degree relatives of thirty (8.69%) patients had a history of epilepsy, while 176 (51%) patients had a family history of febrile seizure. Two hundred and seventy-five patients (79.7%) found to have an infection, most frequently upper respiratory tract infection (53.8%), during the examination, which might cause fever. One hundred and ninety-five patients were followed without treatment, while 48.6% of the patients were treated with rectal diazepam, 23.3% with sodium valproate, 23.3% with levetiracetam and 4.6% with phenobarbital. At the end of the one-year follow-up, only four patients (1.15%) with complex febrile seizure were diagnosed with epilepsy. The age of the onset of febrile seizures, family history of febrile seizures, short episodes of febrile seizure and the presence of epilepsy in the family history were found to be the significant risk factors for repetitive seizures. CONCLUSION: Febrile seizures are generally benign and have a low risk of developing epilepsy. Determining the risk factors is essential for the treatment and follow-up plan.
Current Opinion in Pediatrics · 1991 · 0 citations
Pediatric epilepsy
AbstractThis report reviews recent advances in seizure disorders in children. Correct diagnosis and classification of epilepsies aid in their work-up and management. Patients with a first unprovoked seizure do not need antiepileptic treatment. Children in status epilepticus need aggressive therapy starting with a benzodiazepine, preferably lorazepam. Febrile seizures usually do not require treatment. If indicated, phenobarbital is a safe and effective medication, but it does have significant side effects, including cognitive impairment. The side effects of newer antiepileptic medications are now recognized. Surgery may have an important role in the treatment of intractable seizure disorders.
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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