DeCure for Generalized epilepsy with febrile seizures plus, type 2
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for generalized epilepsy with febrile seizures plus, type 2 — screening already-approved drugs against its 2-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 2 maps to a 2-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
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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 generalized epilepsy with febrile seizures plus, type 2 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 1 (SCN1A) — SCN1A 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 7DTD · 3.3 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
Generalised epilepsy with febrile seizures plus type 2 is a genetic epilepsy syndrome, but the available abstracts do not report any trial of a specific drug for that precise condition. The management literature for febrile seizures in general states that both continuous and intermittent anticonvulsant therapy can prevent single febrile seizures, but side effects may outweigh benefits, so treatment is indicated only in very selected patients (2009 LICE Task Force). In a 2019 cohort of 345 children with febrile seizures, 48.6% received rectal diazepam, 23.3% sodium valproate, 23.3% levetiracetam, and 4.6% phenobarbital; after one year only four patients (1.15%) with complex febrile seizure had developed epilepsy. The same study found that age at onset, family history of febrile seizures, short episodes, and family history of epilepsy were significant risk factors for repetitive seizures.
Outcome data for idiopathic generalised epilepsy syndromes in adults come from a Glasgow cohort of 118 patients (13% of 890 epilepsy cases). Remission was achieved in 64% (66 of 103 with known outcomes). Sodium valproate had a responder rate of 66% versus 45% for lamotrigine, and the difference was significant in juvenile myoclonic epilepsy (75% vs 39%, p=0.014). A history of febrile seizures was the only factor associated with reduced likelihood of remission (p=0.032). In a separate study of 155 adults with complex partial seizures, 9% had a history of febrile seizures, and those with prolonged or recurrent febrile seizures had poorer seizure control.
No abstract reports a drug tested specifically in generalised epilepsy with febrile seizures plus type 2. The 2012 review on antiepileptogenesis targets notes that current anticonvulsants influence only acute ictogenesis and that no reliable biomarkers of epileptogenesis exist; it calls for disease-modifying therapies that prevent the emergence of spontaneous recurrent seizures. What is missing is a dedicated clinical trial in patients with a confirmed SCN1A or other genetic diagnosis for this syndrome, adequate funding for such a trial, and a design that stratifies by genotype and distinguishes prophylaxis of febrile seizures from prevention of later afebrile 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.
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.
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.
Current Opinion in Neurology · 1998 · 67 citations
Febrile seizures: genetics and relationship to other epilepsy syndromes
AbstractThe relationship between febrile seizures and epilepsy has long been debated. We argue that there is some specificity to the types of epilepsy that follow febrile seizures, rather than febrile seizures being a nonspecific marker of a lowered seizure threshold. The relationship between febrile seizures and later epilepsy is frequently genetic. Recent clinical and molecular genetic studies suggest that there are a number of syndrome-specific genes for febrile seizures.
Febrile seizures in patients with complex partial seizures
AbstractFebrile seizures occurred in 14 of 155 (9%) out-patients with complex partial seizures. Twelve patients had prolonged or recurrent febrile seizures, convulsive status epilepticus or a transient postictal neurological deficit. Febrile seizures were associated with perinatal abnormalities, an earlier onset of epilepsy and with a poor seizure control. Recurrent febrile seizures or those with complicating features are associated with an unfavourable therapeutic outcome in adult patients with complex partial seizures.
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.
Child Neurology Open · 2021 · 10 citations · open access
Utility and Safety of Perampanel in Pediatric FIRES and Other Drug-Resistant Epilepsies
AbstractPerampanel is a novel antiepileptic drug, which antagonises AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) glutamate receptor. We describe perampanel as an adjunctive treatment for FIRES (febrile infection-related epilepsy syndrome) and other drug-resistant epilepsies. A single-centre, observational, retrospective study involving 20 pediatric patients was conducted. Perampanel was started for three patients with FIRES, achieving seizure cessation in two patients within a day and on days 19 and 32 of illness. Doses used ranged from 4 to 12 mg/day, without any adverse effects reported or discontinuation of therapy. Responder-rate for other drug-resistant epilepsies is 25%. Median time to achieve ≥50% seizure reduction was 80 days (range: 26-326 days). Adverse effect reported in 47% of the patients includes central nervous system-related, and thrombocytopenia. Eight patients discontinued perampanel, because of ineffectiveness or adverse effects. The median time on perampanel before discontinuation was 179 days (range: 94-345 days). Perampanel may be of benefit in pediatrics FIRES and is of utility in other drug-resistant epilepsies.
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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