DeCure's autonomous Neuro AI scientist is researching a drug-repurposing hypothesis for epilepsy — screening already-approved drugs against its 50-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleEpilepsy maps to a 50-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
approvedTopiramateApproved drug
Structures already discussed alongside epilepsy in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
Human carbonic anhydrase II — Topiramate has a real, experimentally solved structure in complex with this target (PDB 3HKU, 1.8 Å). This is the drug's own deposited structure, not a prediction, and confirms it is a structurally characterised molecule rather than an untested guess.
Loading structure…
helix sheet tordrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 3HKU · 1.8 Å · ligand Topiramate (TOR). Experimental structure, not a prediction.
What the evidence adds up to
About 20% to 30% of epilepsy patients have intractable or uncontrolled seizures despite new antiepileptic drugs. A 2019 study constructed an epilepsy drug-target network using causative genes from 60 epilepsy patients and found that the causative genes of most intractable patients were not targets of existing antiepileptic drugs and were far from the drugs’ etiological mechanisms in functional networks. The authors suggested that drugs targeting those causative genes could be candidates for refractory patients, but no such drugs were tested in the study.
Epileptogenesis is the process by which the brain undergoes molecular and cellular alterations after an insult such as traumatic brain injury, stroke, or cerebral infection, eventually leading to recurrent spontaneous seizures. Only a subpopulation of patients with any of these insults develops epilepsy. Two challenges are identifying patients at risk and preventing or modifying epileptogenesis. Target identification for antiepileptogenic treatments is difficult in humans because patients undergoing epileptogenesis cannot currently be identified, so animal models are necessary. Work is ongoing to determine whether the molecular mechanisms, network alterations, and temporal progression of epileptogenesis depend on the etiology.
Epilepsy surgery is a highly effective and durable treatment for specific types of drug-resistant epilepsy such as temporal lobe epilepsy, with excellent short-term results and increasing information on long-term outcomes including seizure outcome, social and psychiatric outcomes, complications, and mortality. A 2015 article proposed an outcome-centered approach to bridge gaps between treatment options, quality measures, and clinical goals, but did not report new trial results. A 2024 review noted that management of epilepsy patients is a serious problem and that in some countries drugs of unproven effectiveness and feasibility are used.
What is still missing are large, controlled clinical trials testing specific repurposed drugs in well-characterised patient subgroups, particularly those with identified causative genes not targeted by existing antiepileptic drugs. The inability to identify patients undergoing epileptogenesis in humans blocks antiepileptogenic drug development. Funding for such trials and for the necessary patient stratification by genetic and aetiological factors remains insufficient.
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 · 2007 · 214 citations · open access
Epileptogenesis in Experimental Models
AbstractEpileptogenesis refers to a phenomenon in which the brain undergoes molecular and cellular alterations after a brain-damaging insult, which increase its excitability and eventually lead to the occurrence of recurrent spontaneous seizures. Common epileptogenic factors include traumatic brain injury (TBI), stroke, and cerebral infections. Only a subpopulation of patients with any of these brain insults, however, will develop epilepsy. Thus, there are two great challenges: (1) identifying patients at risk, and (2) preventing and/or modifying the epileptogenic process. Target identification for antiepileptogenic treatments is difficult in humans because patients undergoing epileptogenesis cannot currently be identified. Animal models of epileptogenesis are therefore necessary for scientific progress. Recent advances in the development of experimental models of epileptogenesis have provided tools to investigate the molecular and cellular alterations and their temporal appearance, as well as the epilepsy phenotype after various clinically relevant epileptogenic etiologies, including TBI and stroke. Studying these models will lead to answers to critical questions such as: Do the molecular mechanisms of epileptogenesis depend on the etiology? Is the spectrum of network alterations during epileptogenesis the same after various clinically relevant etiologies? Is the temporal progression of epileptogenesis similar? Work is ongoing, and answers to these questions will facilitate the identification of molecular targets for antiepileptogenic treatments, the design of treatment paradigms, and the determination of whether data from one etiology can be extrapolated to another.
Cochrane Database of Systematic Reviews · 2008 · 36 citations
Topiramate add-on for drug-resistant partial epilepsy
AbstractBACKGROUND: The majority of people with epilepsy have a good prognosis and their seizures are controlled by a single antiepileptic drug. However, up to 20% of patients from population-based studies and up to 30% from clinical series (not population-based) develop drug-resistant epilepsy, especially those with partial onset seizures. In this review we summarize the current evidence regarding a new antiepileptic drug, topiramate, when used as an add-on treatment for drug-resistant partial epilepsy. OBJECTIVES: To evaluate the efficacy and safety of topiramate when used as an add-on treatment for drug-resistant partial epilepsy. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group Specialized Register (10 May 2007); the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3, 2007). No language restrictions were imposed. We also contacted the manufacturers of topiramate and researchers in the field to see any ongoing or published studies. SELECTION CRITERIA: Randomized placebo controlled add-on trials of topiramate recruiting people with drug-resistant partial epilepsy. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion and extracted the relevant data. The following outcomes were assessed: (a) 50% or greater reduction in seizure frequency; (b) treatment withdrawal (any reason); (c) side effects. Primary analyses were intention-to-treat. Summary relative risks (RR) with 95% confidence intervals (95% CI) are presented. Dose response was evaluated in regression models. MAIN RESULTS: Ten trials were included representing 1312 randomized participants. Baseline phases ranged from 4-12 weeks and double-blind phases from 11-19 weeks. The RR for a 50% or greater reduction in seizure frequency compared to placebo was 2.85 (95% CI 2.27 to 3.59). Dose regression analysis shows increasing effect with increasing dose, but found no advantage for doses over 300 or 400 mg per day. The RR for treatment withdrawal compared to placebo was 2.26 (95% CI 1.55 to 3.31). The RR for the following side effects indicate that they are significantly associated with topiramate: ataxia 1.95 (99% CI 1.04 to 3.65); dizziness 1.55 (99% CI 1.08 to 2.22); fatigue 2.19 (99% CI 1.43 to 3.35); nausea 2.35 (99% CI 1.28 to 4.29); somnolence 2.18 (99% CI 1.47 to 3.21) and 'thinking abnormally' 5.77 (99% CI 2.50 to 13.35). AUTHORS' CONCLUSIONS: Topiramate has efficacy as an add-on treatment for drug-resistant partial epilepsy. However, trials reviewed were of relatively short duration, and provide no evidence for the long-term efficacy of topiramate. Results cannot be extrapolated to monotherapy or treating other epilepsy types.
Systematic Approach for Drug Repositioning of Anti-Epileptic Drugs
AbstractEpilepsy is a central neurological disorder affecting individuals of all ages and causing unpredictable seizures. In spite of the improved efficacy of new antiepileptic drugs and novel therapy, there are still approximately 20%~30% of patients, who have either intractable or uncontrolled seizures. The epilepsy drug-target network (EDT) is constructed and successfully demonstrates the characteristics and efficacy of popularly used AEDs through the identification of causative genes for 60 epilepsy patients. We discovered that the causative genes of most intractable patients were not the targets of existing AEDs, as well as being very far from the etiological mechanisms of existing AEDs in the functional networks. We show that the existence of new drugs that target the causative genes of intractable epilepsy patients, which will be potential candidates for refractory epilepsy patients. Our systematic approach demonstrates a new possibility for drug repositioning through the combination of the drug-target and functional networks.
Understanding epileptogenesis from molecules to network alteration
AbstractEpilepsy is characterized by recurrent seizures. Following an initial insult, a latent period precedes the onset of spontaneous seizures, a process referred to as epileptogenesis. This period plays a critical role in halting the progression toward epilepsy before the onset of abnormal molecular and network alterations. In this study, the fundamental concepts of epileptogenesis as well as the associated molecular and cellular targets are reviewed.
Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques · 2012 · 2 citations · open access
Outcomes after Epilepsy Surgery
AbstractEpilepsy surgery is a highly effective and durable treatment for specific types of drug resistant epilepsy such as temporal lobe epilepsy. assessment of outcomes is essential in epilepsy surgery, which is an irreversible intervention for a chronic condition. Excellent short-term results of resective epilepsy surgery have been established. In the last years more information regarding long term outcomes have been published. This article reviews the best available evidence about the best measures to assess outcomes and the most important evidence. The outcomes reviewed in this article are the following: seizure outcome, social and psychiatric outcomes, complications and mortality.
Outcome-centered antiepileptic therapy: Rate, rhythm and relief.
AbstractClinicians who manage patients with epilepsy are expected to assess the relevance of clinical trial results to their practice, integrate new treatments into the care algorithm, and implement epilepsy quality measures, with the overall goal of improving patient outcomes. A disease-based clinical framework that helps with choice and combinations of interventions facilitates provision of efficient, cost-effective, and high-quality care. This article addresses the current conceptual framework that informs clinical evaluation of epilepsy, explores gaps between development of treatment options, quality measures and clinical goals, and proposes an outcome-centered approach that bridges these gaps with the aim of improving patient and population-level clinical outcomes in epilepsy.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
THE VALUE OF NEUROPEPTIDES IN THE TREATMENT OF PATIENTS WITH COGNITIVE DYSFUNCTION IN EPILEPSY
AbstractManagement of patients with epilepsy is a serious problem of modern medicine Lack of timely and adequate treatment of patients with epilepsy leads to the occurrence of irreversible anatomical and functional changes in the brain. To improve the effectiveness of treatment of patients with epilepsy in our country, drugs are used, the effectiveness and feasibility of many of which are not reliably proven.
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.
