DeCure for Epilepsy with generalized tonic-clonic seizures
DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for epilepsy with generalized tonic-clonic seizures — screening already-approved drugs against its 46-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEpilepsy with generalized tonic-clonic seizures maps to a 46-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 epilepsy with generalized tonic-clonic seizures 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
carbonic anhydrase 2 (CA2) — CA2 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 hydroxymercurydrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3K34 · 0.9 Å · ligand 4-(HYDROXYMERCURY)BENZOIC ACID (HGB). Experimental structure, not a prediction.
What the evidence adds up to
In a 1987 community-based and prospective hospital study, roughly three-quarters of newly diagnosed epilepsy patients achieved prolonged remission on then-available medication. The first two years of treatment were judged crucial; the longer seizures continued, the less likely control became. Factors linked to chronic epilepsy included brain lesions, neuropsychiatric handicaps, and poor compliance. The same review found no significant differences in efficacy between major antiepileptic drugs, so choice was driven by cost and side effects, particularly cognitive and behavioural ones. The authors noted that most patients with a single unprovoked tonic-clonic seizure went on to develop epilepsy, and that information on the natural history of untreated epilepsy and the possible influence of drugs on spontaneous remission was lacking.
A 1984 survey of 151 patients with partial seizures evolving to secondarily generalised tonic-clonic seizures found that this seizure type accounted for 32.1% of 470 epileptic outpatients at one Japanese hospital. Among 142 successfully followed patients, the rate of complete seizure remission was 42.3%. In 124 patients with both initial and follow-up EEGs, the rate of complete EEG improvement was only 12.1%. These numbers illustrate that even under modern treatment, a substantial proportion of patients with this seizure type did not achieve full remission, and EEG normalisation was uncommon.
A 2014 review of newer anti-epileptic drugs for focal-onset seizures (with or without secondary generalised tonic-clonic seizures) summarised drugs approved as adjunct treatment in the preceding decade. It described their mechanisms of action, dosing schedules, and side effects, but did not report any new efficacy or remission data from the 2012 NICE guideline update it referenced.
What remains missing is systematic data on the natural history of untreated epilepsy, the long-term effect of early drug therapy on the likelihood of spontaneous remission, and prospective trials that stratify patients by seizure type and underlying brain pathology rather than lumping all generalised tonic-clonic seizures together. Funding for such natural-history studies and for trials that separate patients with secondarily generalised seizures from those with primary generalised seizures is still inadequate.
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 · 1987 · 150 citations
Early Treatment and Prognosis of Epilepsy
AbstractSummary: Community‐based studies and our own prospective hospital‐based studies suggest that the prognosis for control of epilepsy is more favorable than previously reported. Approximately three quarters of newly diagnosed patients can enter prolonged remission on currently available medication. The first 2 years of treatment are crucial in determining the subsequent course of epilepsy. The longer seizures continue, the less likely they are to be controlled. Factors that contribute to the evolution of chronic epilepsy are the presence of brain lesions, neuropsychiatric handicaps, and poor compliance. Early effective treatment may also be important in preventing the evolution of chronic epilepsy. Recent studies have not revealed any significant differences in efficacy between the major antiepileptic drugs, and the choice of drug will therefore be influenced by costs and side effects, especially cognitive and behavioral effects. The majority of patients with a single unprovoked tonic‐clonic seizure go on to develop epilepsy. Studies are required to evaluate the need for and outcome of therapy in such patients. Information about the natural history of untreated epilepsy, and also the possible influence of drug therapy on the prospects for spontaneous remission, is lacking. RESUMEN Los estudios comunitarios y nuestros propios estudios prospectivos practicados en el hospital surgieren que el pronóstico del control de epilepsyía es más favorable de lo que se ha publicado previamente. Aproximadamente tres cuartos de enfermos nuevos pueden presentar una remisión prolongada con la medicación disponible actualmente. Los dos primeros años de tratamiento son cruciales para determinar el curso subsiguiente de la epilepsyía. A medida que los ataques se repiten las posibilidades de su control son más escasas. Los factores que contribuyen para que se establezca una evolución cronica de la epilepsyía son la presencia de lesiones cerebrales, los trastornos neuropsiquiátricos y la poca fiabilidad de los pacientes. Un tratamiento precoz eficaz puede también ser importante para evitar la evolución crónica de la epilepsyía. Estudios recientes no han revelado nigguna diferencia significativa con respecto a la eficacia entre las drogas antiepilépticas más importantes, por lo que la elección de una medicación deberá ser realizada teniendo en cuenta los costes y los efectos colaterales, especialmente en lo que respecta a la capacidad cognitiva y los efectos en el comportamiento del enfermo. La mayoría de los pacientes con un sólo ataque espontáneo tónico‐clónico desarrollan una epilepsyía subsiguiente. En estos casos son necesarios estudios especiales para valorar la necesidad de iniciar un tratamiento y los resul‐tados de tal terapia. En el momento actual falta información acerca de la historia natural de la epilepsyía no tratada y también acerca de la posible influencia de la terapia medicamentosa sobre las posibilidades de remisiones espontáneas. ZUSAMMENFASSUNG Ambulante Untersuchungen und unsere eigene prospektive Krankenhausstudie weisen auf eine bessere Prognose der Epilepsie bezügl. Anfallsfreiheit als bisher angenommen hin. Fast dreiviertel aller neu diagnostizierten Patienten können einer langanhaltenden Anfallsfreiheit unter den üblichen Medikamenten zugeführt werden. Die ersten zwei Behandlungsjahre sind für den weiteren Verlauf der Epilepsie entscheidend. Je länger die Anfälle anhalten, desto weniger wahrscheinlich wird Anfallsfreiheit erreicht. Faktoren, die eine chronische Epilepsie begünstigen, sind Hirnschädigung, neuropsychiatrische Störungen und schlechte Compliance. Eine frühe, effektive Behandlung kann die Entwicklung einer chronischen Epilepsie verhindern. Jüngere Studien haben keine signifikanten Unterschiede in der Effektivität der verschiedenen Haupt‐Antiepileptika gefunden, so daß die Wahl des Medikaments vielmehr durch seine Kosten und Nebenwirkungen–vor allem im cognitiven und Verhaltensbereich–beeinflußt wird. Die meisten Patienten mit einem einzigen, nicht provozierten Grand mal entwickeln eine Epilepsie. Weitere Untersuchungen sind erforderlich, um gerade bein diesen Patienten die Notwendigkeit und den Verlauf der Therapie zu beurteilen. Es fehlen Berichte über den natürlichen Verlauf unbehandelter Epilepsien und den Einfluß der Pharmako‐Therapie auf mögliche Spontanremission. RÉSUMÉ Des études de population et nos propres études prospectives effectuées en milieu hospitaller suggèrent que le pronostic du contrôle de ľépilepsie est plus favorable que ce qui avait été rapporté antérieurement. Environ 75% des patients nouvellement diagnostiqués obtiennent une rémission prolongée au moyen des médications actuellement disponibles. Les deux premières années du traitement sont décisives pour ľévolution ultérieure de ľépilepsie. Plus les crises persistent, moins elles ont de chances ď;être contrôlées par la suite. Les facteurs qui contribuent à la chronicisation de ľépilepsie sont ľexistence de lésions cérébrales, de handicaps neuropsychiatriques, et une mauvaise compliance au traitement. Un traitement précoce efficace peut aussi jouer un rô1e important dans la prévention ď;une chronicisation de ľépilepsie. Des travaux récents n'ont pas montré de différence significative dans ľefficacité des antiépileptiques majeurs, et le choix du médicament sera influenceé surtout par les considérations de prix et ď;effets secondaires, surtout cognitifs et comportementaux. La majorité des patients présentant une crise tonicoclonique spontanée unique développent une épilepsie chronique. Des études sont nécessaires pour évaluer la nécessité et le bénéfice ď;un traitement chez de tels patients. Nous manquons ď;informations sur ľévolution spontanée ď;une épilepsie non traitée et sur ľinfluence possible du traitement médicamenteux sur les perspectives de rémission spontanée.
Psychiatry and Clinical Neurosciences · 1984 · 0 citations
Natural History and Prognosis of Partial Seizures Evolving to Secondarily Generalized Tonic‐Clonic Seizures
AbstractAbstract: A survey was conducted in order to obtain reliable information on the natural history and prognosis of partial seizures evolving to secondarily generalized tonic‐clonic seizures (GTC) under a modern treatment approach. One‐hundred and fifty‐one patients have had partial seizures evolving to secondarily GTC and the rate of patients with this seizure type was 32.1% out of 470 epileptic patients in the Outpatient Clinic of the Department of Neuropsychiatry, Kanazawa University Hospital, in 1982. Out of the 151, 142 patients were successfully followed up. The rate of complete remission of seizures in those patients was 42.3%. The number of patients who were successfully followed up in the initial EEG and the present EEG together were 124 cases. The rate of complete improvement of EEG findings in those cases was 12.1%.
British Journal of Neuroscience Nursing · 2014 · 0 citations
Newer drug treatments for focal-onset epilepsy
AbstractOver the past decade many new anti-epileptic drugs have been approved as adjunct treatment for people with epilepsy experiencing focal-onset seizures with or without secondary generalised tonic-clonic seizures. The 2012 update of the 2004 National Institute for Health and Care Excellence Clinical Guideline 20 evaluated the efficacy and cost-effectiveness of the newer anti-epileptic drugs. This article provides an overview of some of these drugs and their use in the management of focal-onset seizures, including their mechanism of action, dosing schedule and side-effects.
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.
