DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for Dravet syndrome — screening already-approved drugs against its 31-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleDravet syndrome maps to a 31-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 dravet syndrome 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 beta subunit 1 (SCN1B) — SCN1B 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…
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RCSB Protein Data Bank · entry 7W9K · 2.2 Å · ligand O-[(R)-{[(2R)-2,3-bis(octadecanoyloxy)propyl]oxy}(hydroxy)phosphoryl]-L-serine (P5S). Experimental structure, not a prediction.
What the evidence adds up to
Dravet syndrome is a severe genetic epileptic encephalopathy caused by mutations in the SCN1A sodium channel gene. In a Turkish cohort of nine patients, five had nonsense mutations, two had missense mutations, one had a splice site mutation, and one had a deletion mutation; three of these mutations had not been previously described. Seizures began after whole cell pertussis vaccination in all nine patients. Seizures ceased in only one patient and continued in the other eight. Developmental regression was severe in three patients, with frequent status epilepticus. The type of mutation did not predict disease severity. In a separate genetic analysis of fraternal twins, a heterozygous c.5348C>T (p.Ala1783Val) variant of SCN1A was identified; the father was found to carry the mutation in mosaic form in both peripheral blood and semen, indicating paternal mosaicism as the genetic cause. Among eight Lebanese cases referred for molecular analysis, seven had positive results with de novo heterozygous variants in different exons, and four variants were novel. Overall, 70–80% of patients have SCN1A mutations.
Seizure control is difficult to achieve. Valproate, benzodiazepines and stiripentol may cause improvement, whereas sodium channel blockers such as lamotrigine and carbamazepine may aggravate seizures. A 2025 retrospective German study of 22 patients (median age 8.9 years, range 2.2–26.7) treated with fenfluramine plus potassium bromide found a responder rate for seizure reduction of 68.4% at 3 months and 76.9% at 6 months. However, adverse events occurred in 68.2% of patients, most commonly somnolence (59.1%) and loss of appetite (22.7%). In 40.9% of patients either fenfluramine or potassium bromide was discontinued due to sedation. When potassium bromide doses were not reduced, serum bromide levels increased significantly after fenfluramine initiation, contributing to these adverse events. The authors recommend close monitoring of bromide levels and early dose reduction.
What is still missing are prospective, randomised controlled trials that test fenfluramine combined with potassium bromide against either drug alone, with standardised dose adjustment protocols and systematic adverse event reporting. The genetic heterogeneity of SCN1A mutations and the lack of a clear genotype–phenotype correlation mean that patient stratification for any drug trial remains difficult. No therapy has been shown to reverse developmental regression, and long-term outcome data beyond six months for the fenfluramine–bromide combination are not available.
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 Indian Academy of Neurology · 2011 · 5 citations · open access
Severe myoclonic epilepsy of infancy (Dravet syndrome): Clinical and genetic features of nine Turkish patients
AbstractPURPOSE: Mutations of the α-1 subunit sodium channel gene (SCN1A) cause severe myoclonic epilepsy of infancy (SMEI). To date, over 300 mutations related to SMEI have been described. In the present study, we report new SCN1A mutations and the clinical features of SMEI cases. MATERIALS AND METHODS: We studied the clinical and genetic features of nine patients diagnosed with SMEI at the Pediatric Neurology Department of Istanbul Medical Faculty. RESULTS: Five patients had nonsense mutations, two had missense mutations, one had a splice site mutation and one had a deletion mutation of the SCN1A gene. Mutations at c.3705+5G splice site, p.trip153X nonsense mutation and deletion at c.2416_2946 have not been previously described. The seizures started following whole cell pertussis vaccination in all patients. The seizures ceased in one patient and continued in the other eight patients. Developmental regression was severe in three patients, with frequent status epilepticus. The type of mutation was not predictive for the severity of the disease. Two of the three patients with severe regression had nonsense and missense mutations. CONCLUSIONS: Dravet syndrome can be result of several different types of mutation in SCN1A gene. Onset of the seizures after pertussis vaccination is an important clue for the diagnosis and neuro- developmental delay should be expected in all patients.
Tidsskrift for Den norske legeforening · 2012 · 2 citations · open access
Dravets syndrom som årsak til epilepsi og utviklingshemning
AbstractBACKGROUND: Dravet syndrome is a severe, genetic epileptic encephalopathy with seizures starting during the first year of life. We present a review of the genetic and clinical picture along with treatment aspects. MATERIAL AND METHODS: This review is based on a non-systematic literature search in PubMed until April 2011 and the personal experiences of the authors. RESULTS: Dravet syndrome should be suspected in children with febrile hemiconvulsions or tonic-clonic seizures in the first year of life. Non-febrile seizures also occur, and other seizure types gradually appear, e.g. myoclonic jerks, atypical absences or focal seizures. In adulthood the clinical picture is less characteristic. The clinical diagnosis is supported by genetic testing; 70-80% of the patients have mutations in the sodium channel subunit gene SCN1A. Seizure control is difficult to achieve, but valproate, benzodiazepines and stiripentol may cause improvement, whereas sodium channel blockers, such as lamotrigine and carbamazepine may aggravate the tendency towards seizures. INTERPRETATION: Dravet syndrome appears to be an under-recognised condition among both children and adults with severe epilepsy and learning disability. Clinical information from the first years of life is essential in making the diagnosis. A correct diagnosis at an early age is essential for appropriate treatment and genetic counselling.
Efficacy and tolerability of fenfluramine with concomitant potassium bromide in patients with Dravet syndrome
AbstractOBJECTIVE: To assess the efficacy and tolerability of fenfluramine (FFA) with concomitant potassium bromide (BR) in patients with Dravet syndrome (DS). METHODS: This multicenter retrospective study, conducted within the German compassionate use program, analyzed BR doses and serum levels before and after FFA initiation, adverse events (AEs), seizure reduction, and symptoms changes using the Clinical Global Impression of Change (CGIC) scale. Timepoints were defined as T0 (baseline), T1 (FFA initiation), T2 and T3 (first and second BR level measurement after FFA initiation). RESULTS: Twenty-two patients (median age 8.9 years, range 2.2-26.7) treated with BR were included. Median duration of BR-FFA combination therapy was 7 months (range 0-28). BR doses were reduced at least once in 11 patients (50%) as a precaution or because of increased serum levels. At T3, mean BR dose was significantly lower compared to T0 (1217 mg/day, SD = 699 vs. 1755 mg/day, SD = 752.2; p = 0.04), but BR levels showed no significant difference between T2 or T3 and baseline. In contrast, for patients with stable BR doses (n = 14), mean BR level significantly increased from baseline (1376 mg/L, SD = 345.7) to T2 (1762 mg/L, SD = 553.3; p = 0.04). AEs were reported in 15 patients (68.2%) during the combination therapy, with the most common being somnolence (59.1%) and loss of appetite (22.7%). In 40.9% either FFA or BR were discontinued due to sedation. The responder rate for seizure reduction was 68.4% at 3 months and 76.9% at 6 months. SIGNIFICANCE: BR levels increased significantly after FFA initiation when BR doses were not reduced, contributing to adverse events-primarily somnolence-and resulting in the discontinuation of BR or FFA in some patients. Close monitoring of BR levels is crucial to minimize the risk of adverse events. PLAIN LANGUAGE SUMMARY: This study investigated the combination of fenfluramine (FFA) and potassium BR in treating Dravet syndrome. It was found that it is effective in reducing seizures, but BR levels often went up after starting FFA, which caused side effects like drowsiness in many patients. In some cases, these side effects were serious enough that physicians had to stop either BR or FFA. The study highlights the need for careful monitoring of BR levels when using this combination to avoid potential side effects by reducing the BR dose early if needed.
[Genetics Analysis of patients with Dravet syndrome due to mosaicism variation of paternal SCN1A gene].
AbstractGenetic analysis was performed on a family of fraternal twins affected with Dravet syndrome by genetic tests whose parents were normal. To further analyze the cause of the disease, the fraternal twins were subjected to whole exome sequencing (WES), and the family was verified by Sanger sequencing, with the father semen and peripheral blood DNA were further analysed by target sequencing. The WES test identified a heterozygous c.5348C>T (p.Ala1783Val) variant of the SCN1A gene in the fraternal twins, which was predicted to be pathogenic and was detected in the father peripheral blood and semen, but not in the mother. So the mosaicism mutation of paternal SCN1A gene might be the genetic cause of Dravet syndrome in offspring.
Los archivos municipales de la provincia de Valladolid
AbstractDravet syndrome, also known as severe myoclonic epilepsy in infancy, is a rare disease characterized by the appearance of different types of seizures in a healthy baby, triggered by various factors and stressful events. We report 8 Lebanese cases referred for molecular analysis of the <i>SCN1A</i> gene. Results were positive in 7 cases and revealed de novo variants at the heterozygous state in different exons of the gene for all except one, where the variant was intronic. Four variants were novel. Confirmation of Dravet syndrome is important for a better follow-up and treatment, preventing the occurrence of status epilepticus and severe neurological deterioration.
Mutation analysis of the SCN1A gene for suspected Dravet syndrome/GEFS+ – High detection yield, unsatisfactory prognostic value
AbstractAims: Dravet syndrome comprises severe myoclonic epilepsies starting in the late first year of life which are difficult to treat and show a poor developmental prognosis. Since 2001 mutations in the SCN1A gene are known to cause Dravet syndrome and the closely related GEFS+. Molecular analysis may confirm the clinical diagnosis, though some cases bear marked difficulties in DNA data interpretation.
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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