DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for familial temporal lobe epilepsy 7 — 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 moduleFamilial temporal lobe epilepsy 7 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
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 temporal lobe epilepsy 7 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.
What the evidence adds up to
In a 2011 study of 42 children who underwent temporal lobe resection for drug-resistant epilepsy, 86% were seizure-free after an average follow-up of 9 years, and 57% had stopped antiepileptic medication. A significant increase in IQ was seen in the surgical group after more than 5 years, but not in a matched nonsurgical comparison group of 11 children. The IQ increase was linked to stopping medication and changes in MRI-derived grey matter volume. Better psychosocial outcome and quality of life were more strongly associated with seizure freedom than with surgery itself.
A separate 2012 study of 257 paediatric epilepsy surgery patients with five-year follow-up data found that 53% were continuously seizure-free, 18% had late seizure recurrence, 3% became seizure-free after initial failure, and 25% were never seizure-free. Five-year outcomes improved over time: 68% of patients operated between 2001 and 2005 were continuously seizure-free, compared with 36% operated between 1991 and 1995. Among continuously seizure-free patients, 55% were not taking antiepileptic drugs. Four late deaths occurred in the not seizure-free group versus one in the seizure-free group.
A 2012 review of genetics in temporal lobe epilepsy states that no genes have been clearly related to the condition despite many linkage and association studies. A 2011 Polish-language review notes that the cause of epilepsy remains unknown in 60–65% of patients, and that genetic predisposition is thought to account for about 40% of idiopathic cases. It cites autosomal dominant nocturnal frontal lobe epilepsy and juvenile myoclonic epilepsy as examples linked to mutations in nicotinic acetylcholine receptor subunit genes.
A 2025 real-world study of 146 paediatric patients with drug-resistant epilepsy given adjunctive clobazam reported response rates of 58.99% at 6 months and 62.41% at 12 months, and seizure-free rates of 36.69% and 35.34% respectively. Retention rates were 87.67% at 6 months and 81.51% at 12 months. Efficacy was better in patients with genetic variants (60.42% responded) and significantly better for the SCN1A genotype than for other genotypes. The independent factor associated with response was a lower baseline seizure frequency (fewer than one seizure per day). Adverse reactions occurred in 16.64% of patients, most commonly excessive salivation and loss of appetite. A separate 2025 case report describes a 12-month-old with DEPDC5-related familial focal epilepsy with variable foci-1 whose seizures were partially responsive to sodium valproate but not to levetiracetam.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Neurology · 2011 · 242 citations · open access
Long-term intellectual outcome after temporal lobe surgery in childhood
AbstractOBJECTIVE: Temporal lobe resection is an established treatment for medication-resistant temporal lobe epilepsy, which in recent years has increasingly been performed in children. However, little is known about the long-term outcome in these children. The aim of this study was to characterize intellectual and psychosocial functioning of children after temporal lobe resection as they progress into late adolescence and adulthood. METHODS: We report the long-term follow-up of 42 children who underwent temporal lobe surgery after an average postoperative period of 9 years. Longitudinal change in IQ was documented, psychosocial outcome including quality of life was assessed, and preoperative and postoperative T1-weighted MRI brain scans were evaluated quantitatively. A well-matched nonsurgical comparison group of 11 children with similar clinical characteristics was also assessed. RESULTS: At follow-up, 86% of the surgical group were seizure-free, and 57% were no longer taking antiepileptic medication. A significant increase in IQ was found in the surgical group after an extended follow-up period of >5 years. This IQ change was not found in the nonsurgical comparison group. IQ increases were associated with cessation of antiepileptic medication and changes in MRI-derived gray matter volume. The surgical group also reported better psychosocial outcome including quality of life, which was more strongly associated with seizure freedom rather than surgery per se. CONCLUSIONS: Surgery for temporal lobe epilepsy performed in childhood results in excellent long-term seizure control and favorable cognitive outcome along with positive effects on brain development. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that temporal lobectomy in children with temporal lobe epilepsy is associated with improved long-term intellectual outcomes compared with those undergoing standard medical treatment.
AbstractBACKGROUND: It is unclear whether long-term seizure outcomes in children are similar to those in adult epilepsy surgery patients. OBJECTIVE: To determine 5-year outcomes and antiepilepsy drug (AED) use in pediatric epilepsy surgery patients from a single institution. METHODS: The cohort consisted of children younger than 18 years of age whose 5-year outcome data would have been available by 2010. Comparisons were made between patients with and without 5-year data (n = 338), patients with 5-year data for seizure outcome (n = 257), and seizure-free patients on and off AEDs (n = 137). RESULTS: Five-year data were available from 76% of patients. More seizure-free patients with focal resections for hippocampal sclerosis and tumors lacked 5-year data compared with other cases. Of those with 5-year data, 53% were continuously seizure free, 18% had late seizure recurrence, 3% became seizure free after initial failure, and 25% were never seizure free. Patients were more likely to be continuously seizure free if their surgery was performed during the period 2001 to 2005 (68%) compared with surgery performed from 1996 to 2000 (61%), 1991 to 1995 (36%), and 1986 to 1990 (46%). More patients had 1 or fewer seizures per month in the late seizure recurrence (47%) compared with the not seizure-free group (20%). Four late deaths occurred in the not seizure-free group compared with 1 in the seizure-free group. Of patients who were continuously seizure free, 55% were not taking AEDs, and more cortical dysplasia patients (74%) had stopped taking AEDs compared with hemimegalencephaly patients (18%). CONCLUSION: In children, 5-year outcomes improved over 20 years of clinical experience. Our results are similar to those of adult epilepsy surgery patients despite mostly extratemporal and hemispheric operations for diverse developmental etiologies.
Epilepsy Research and Treatment · 2012 · 33 citations · open access
Genetics of Temporal Lobe Epilepsy: A Review
AbstractTemporal lobe epilepsy (TLE) is usually regarded as a polygenic and complex disorder. To understand its genetic component, numerous linkage analyses of familial forms and association studies of cases versus controls have been conducted since the middle of the nineties. The present paper lists genetic findings for TLE from the initial segregation analysis to the most recent results published in May 2011. To date, no genes have been clearly related to TLE despite many efforts to do so. However, it is vital to continue replication studies and collaborative attempts to find significant results and thus determine which gene variant combination plays a definitive role in the aetiology of TLE.
Neurologia i Neurochirurgia Polska · 2011 · 2 citations
Zaburzenia czynności kanałów jonowych w patogenezie padaczek idiopatycznych
AbstractPomimo postępów diagnostyki nadal u ok. 60–65% chorych nie można jednoznacznie ustalić przyczyny padaczki. W tej grupie chorych główną rolę odgrywają przypuszczalnie czynniki genetyczne. Uważa się, że u ok. 40% pacjentów predyspozycja genetyczna odpowiada za występowanie padaczek, określanych mianem „idiopatycznych”. Podłoże genetyczne padaczki potwierdzają liczne przykłady rodzinnie występujących zespołów padaczkowych. Należą do nich dziedziczona autosomalnie dominująco padaczka czołowa z napadami nocnymi oraz młodzieńcza padaczka miokloniczna. Obydwie formy padaczek uwarunkowane są mutacjami genów dla podjednostek neuronalnego receptora nikotynowego dla acetylocholiny. Postęp genetyki stworzył szansę dokładniejszego zrozumienia epileptogenezy na poziomie molekularnym, co ułatwia rozpoznanie oraz stwarza bardziej racjonalne podstawy leczenia i zapobiegania tej postaci padaczki. Despite advances in diagnostics, the cause of epilepsy has still not been unequivocally determined in 60-65% of patients. In this group of patients, genetic factors probably play the main role. It is thought that genetic predisposition is responsible for the occurrence of so-called “idiopathic” forms of epilepsy in about 40% of patients. The genetic basis of epilepsy has been substantiated by numerous examples of familial forms of epileptic syndromes. Among these, autosomal dominant nocturnal frontal lobe epilepsy and juvenile myoclonic epilepsy can be mentioned. Mutations in the neuronal nicotinic acetylcholine receptor subunit genes are responsible for both these epilepsies. Recent advances in molecular genetics have provided the means for better understanding of human epileptogenesis at a molecular level, which facilitates clinical diagnosis and provides a more rational basis for therapy and prevention of this form of epilepsy.
Drug Design Development and Therapy · 2025 · 0 citations · open access
Efficacy and Safety of Clobazam Adjunctive Therapy in Pediatric Patients with Drug-Resistant Epilepsy
AbstractObjective: To determine the efficacy and safety of clobazam, a benzodiazepine derivative endorsed for adjunctive therapy in drug-resistant epilepsy due to its broad-spectrum efficacy and tolerability profile, as an adjunctive treatment for pediatric patients with drug-resistant epilepsy. Methods: This was a multicenter, real-world, self-controlled study. Pediatric drug-resistant epilepsy patients receiving clobazam adjunctive treatment at three centers were retrospectively included. The primary outcomes were response rates and seizure-free rates at 6 and 12 months of treatment. The secondary outcomes included retention rates at months 6 and 12 of treatment and adverse events that occurred during the addition of clobazam therapy. Results: A total of 146 patients were included. The retention rates were 87.67% (128/146) and 81.51% (119/146) at 6 and 12 months, respectively. The response rates were 58.99% (82/139) and 62.41% (83/133), and the seizure-free rates were 36.69% (51/139) and 35.34% (47/133) at 6 and 12 month, respectively. Clobazam has shown good efficacy in patients with epilepsy due to genetic variants (60.42%, 29/48) and its significantly better efficacy for the SCN1A genotype than for other genotypes (P=0.048). The independent factor associated with clinical response was a lower baseline seizure frequency (seizure frequency <1 seizure/day). Adverse reactions occurred in 24 (24/146, 16.64%) patients, with excessive salivation/hypersalivation (4/146, 2.74%) and loss of appetite (4/146, 2.74%) being the most common. Conclusion: Clobazam adjunctive therapy is effective, safe and well tolerated in pediatric patients with drug-resistant epilepsy.
DEPDC5-Related Familial Focal Epilepsy With Variable Foci-1: A Report of a Rare Case
AbstractFamilial focal epilepsy with variable foci-1 (FFEVF1) is a genetic epilepsy syndrome associated with a pathogenic mutation in the DEPDC5 gene. It has autosomal dominant inheritance, along with incomplete penetrance and a variable phenotype. We present a case of focal seizures that progressed to generalized tonic-clonic seizures within the span of one year in a 12-month-old male child. A family history of epilepsy was present in the mother and grandmother of the child. Generalized epilepsy was observed in the initial EEG, while the MRI of the brain was unremarkable. Levetiracetam was unable to control the seizures; however, they were partially responsive to sodium valproate, which was prescribed later. A heterozygous pathogenic variant was revealed in exon 26 during whole-exome sequencing of the DEPDC5 gene. Family history and genetic testing can play crucial roles in pediatric epilepsy diagnosis, particularly when lab investigations and neuroimaging are normal, as showcased in this case.
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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