DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for temporal lobe epilepsy — screening already-approved drugs against its 6-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleTemporal lobe epilepsy maps to a 6-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 temporal lobe epilepsy 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 8 (SCN8A) — SCN8A 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 25II · 2.5 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
A 1992 randomised study of 40 patients undergoing temporal lobectomy for intractable temporal lobe epilepsy compared postoperative carbamazepine monotherapy with continuation of presurgical polytherapy. No significant differences were found between the groups in seizure recurrence rate, type of recurrence, or time to recurrence. Patients on polytherapy had a 30% incidence of drug-related side effects, compared with 10% in the carbamazepine group. The authors concluded that carbamazepine monotherapy is safe after temporal lobectomy and that multiple antiepileptic drugs are not necessary.
A 2004 technical report described temporal lobotomy in 10 patients with drug-resistant complex partial seizures and extensive lobar or hemispheral atrophy on imaging. At last follow-up, seven patients were seizure-free, one had rare seizures, and two had less than a 90% reduction in seizures. One patient who underwent left-sided lobotomy had a postoperative speech fluency deficit. The authors noted these outcomes were similar to those in their overall temporal lobectomy series and called for larger series to better define the procedure’s role.
A 2009 analysis of 125 consecutive patients who underwent standard temporal lobectomy without invasive recording reported long-term outcomes. A 1988 essay noted that surgical operations for intractable temporal lobe epilepsy had been used for over 40 years but that controversy remained about indications and theoretical basis. A 2024 review summarised that temporal lobe epilepsy is largely considered an acquired form developing after neuronal trauma, and that a therapeutic approach to stop epileptogenesis or reliably cure the disease has yet to be developed. The review discussed evidence from excitotoxic rodent models and highlighted recent investigations emphasising the role of genetic background, including variants of neurodevelopmental genes, in the acquisition of epilepsy.
A 2016 study of 24 patients undergoing anterior temporal lobectomy for intractable temporal lobe epilepsy analysed cortical gene expression in relation to baseline seizure frequency. Expression levels of forty genes were significantly associated with baseline seizure frequency. Among the seven most significant, four had been linked to other neurologic diseases. High seizure frequency was associated with low expression of Homeobox A10, Forkhead box A2, Lymphoblastic leukemia derived sequence 1, HGF activator, Kelch repeat and BTB domain containing 11, Thanatos-associated protein domain containing 8, and Heparin sulfate 3-O-sulfotransferase 3A1. The authors described these as novel associations and suggested future investigation could establish new biomarkers. What remains missing is a reliable pharmacological intervention that stops epileptogenesis or cures the disease, as the 2024 review states none has yet been developed. Larger surgical series with consistent outcome reporting, prospective validation of the gene-expression findings in independent patient cohorts, and trials that stratify patients by genetic or molecular markers are still needed.
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 · 1992 · 31 citations
Antiepileptic Drug Treatment After Temporal Lobe Epilepsy Surgery: A Randomized Study Comparing Carbamazepine and Polytherapy
AbstractTemporal lobectomy is an effective treatment in selected patients with medically intractable temporal lobe epilepsy (TLE). Postoperative antiepileptic drug (AED) treatment guidelines have not been established, and patients are often treated with polytherapy postoperatively. We prospectively randomized 40 patients undergoing temporal lobectomy to monotherapy with carbamazepine (CBZ, 20) or to continuation of their presurgical polytherapy (20) to assess the efficacy and safety of each regimen during the first year after operation. No significant differences between groups were noted with respect to seizure recurrence rate and type or time of recurrence. Patients in the polytherapy group had a 30% incidence of drug-related side effects as compared with only 10% in the CBZ group. These results suggest that after temporal lobectomy for intractable epilepsy, patients can be safely treated with CBZ monotherapy and that treatment with multiple AEDs is not necessary.
TEMPORAL LOBOTOMY IN THE SURGICAL MANAGEMENT OF EPILEPSY: TECHNICAL REPORT
AbstractOBJECTIVE: To describe the technique of temporal lobotomy and demonstrate that it may produce results equivalent to anterior temporal lobectomy in the control of drug-resistant complex partial seizures of anterior temporal lobe origin. METHODS: Patient selection and evaluation was similar to that for other patients undergoing anterior temporal lobectomy, with the exception that the 10 selected patients all demonstrated extensive lobar or hemispheral atrophy on magnetic resonance imaging or computed tomographic scans. The lobotomy technique involved posterior and superior disconnection, each of which was broken down into lateral and mesial components. RESULTS: At last follow-up, seven patients were seizure-free, one had rare seizures, and two had a less than 90% decrease in seizures. These outcomes are similar to those in our overall temporal lobectomy series. One patient who underwent left-sided temporal lobotomy had a speech fluency deficit postoperatively. CONCLUSION: Temporal lobotomy seems to be an effective disconnective procedure in the treatment of drug-resistant temporal lobe epilepsy. Larger series will be needed to better define its role in the management of this condition.
British Journal of Neurosurgery · 1988 · 12 citations
Surgical Alternatives for the Treatment of Temporal Lobe Epilepsy
AbstractSurgical operations for the treatment of intractable temporal lobe epilepsy have been used for well over 40 years and yet there is still controversy about both the clinical situation in which these operations are indicated and their theoretical basis. This brief essay is an attempt to explain and resolve some of these difficulties.
Molecular Genetics of Acquired Temporal Lobe Epilepsy
AbstractAn epilepsy diagnosis reduces a patient's quality of life tremendously, and it is a fate shared by over 50 million people worldwide. Temporal lobe epilepsy (TLE) is largely considered a nongenetic or acquired form of epilepsy that develops in consequence of neuronal trauma by injury, malformations, inflammation, or a prolonged (febrile) seizure. Although extensive research has been conducted to understand the process of epileptogenesis, a therapeutic approach to stop its manifestation or to reliably cure the disease has yet to be developed. In this review, we briefly summarize the current literature predominately based on data from excitotoxic rodent models on the cellular events proposed to drive epileptogenesis and thoroughly discuss the major molecular pathways involved, with a focus on neurogenesis-related processes and transcription factors. Furthermore, recent investigations emphasized the role of the genetic background for the acquisition of epilepsy, including variants of neurodevelopmental genes. Mutations in associated transcription factors may have the potential to innately increase the vulnerability of the hippocampus to develop epilepsy following an injury-an emerging perspective on the epileptogenic process in acquired forms of epilepsy.
Pathophysiology · 2016 · 9 citations · open access
Cortical gene expression correlates of temporal lobe epileptogenicity
AbstractINTRODUCTION: Despite being one of the most common neurological diseases, it is unknown whether there may be a genetic basis to temporal lobe epilepsy (TLE). Whole genome analyses were performed to test the hypothesis that temporal cortical gene expression differs between TLE patients with high vs. low baseline seizure frequency. METHODS: Baseline seizure frequency was used as a clinical measure of epileptogenicity. Twenty-four patients in high or low seizure frequency groups (median seizures/month) underwent anterior temporal lobectomy with amygdalohippocampectomy for intractable TLE. RNA was isolated from the lateral temporal cortex and submitted for expression analysis. Genes significantly associated with baseline seizure frequency on likelihood ratio test were identified based on >0.90 area under the ROC curve, P value of <0.05. RESULTS: Expression levels of forty genes were significantly associated with baseline seizure frequency. Of the seven most significant, four have been linked to other neurologic diseases. Expression levels associated with high seizure frequency included low expression of Homeobox A10, Forkhead box A2, Lymphoblastic leukemia derived sequence 1, HGF activator, Kelch repeat and BTB (POZ) domain containing 11, Thanatos-associated protein domain containing 8 and Heparin sulfate (glucosamine) 3-O-sulfotransferase 3A1. CONCLUSIONS: This study describes novel associations between forty known genes and a clinical marker of epileptogenicity, baseline seizure frequency. Four of the seven discussed have been previously related to other neurologic diseases. Future investigation of these genes could establish new biomarkers for predicting epileptogenicity, and could have significant implications for diagnosis and management of temporal lobe epilepsy, as well as epilepsy pathogenesis.
German Medical Science (German Research Foundation) · 2009 · 0 citations · open access
Seizure outcome following standard temporal lobectomy: analysis of 125consecutive patients
AbstractObjective: To analyze long term results of temporal lobe epilepsy surgery without invasive recording and to evaluate preoperative factors predicting good postoperative outcome. Methods: Between October 2000 and October 2007, a total of 125 patients underwent resective surgery for pharmacologically[for full text, please go to the a.m. URL]
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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