Targeting the trunk of multi-root common epilepsy with gene therapy

Molecular Therapy — Methods & Clinical Development, Journal Year: 2025, Volume and Issue: 33(2), P. 101453 - 101453

Published: April 2, 2025

Language: Английский

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Clinical trials of prevention of acquired epilepsy: New proof‐of‐concept approach to restart trials

Epilepsia, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Abstract Approximately 20% of epilepsy is caused by acute central nervous system insults such as traumatic brain injury (TBI), stroke, and infection. There a latent period weeks to years between the insult onset, which offers an opportunity prevent epilepsy. No preventive treatments exist. Their development major unmet need in neurology. For logistical reasons, acquired after TBI, posttraumatic (PTE), most suitable for prevention studies. In past 20 years, preclinical PTE research has flourished, offering potential PTE, but clinical been dormant. The barrier treatment lack viable proof concept (POC) trial design. trials use first late unprovoked seizure outcome measure, necessitates long (~2‐year) follow‐up makes POC studies nonfeasible. A reliable biomarker early detection would allow shorter duration facilitate studies, not yet available. Biomarker, POC, randomized have virtually identical designs terms patient inclusion follow‐up. Done sequentially, take generation complete. We propose novel design that combines discovery biomarker(s) with study uses adaptive POC–phase 3 continuation approach incorporate into phase following interim futility analysis 6 months 25% cohort, population. This establish model prevention, shorten treatment, reopen door

Language: Английский

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Design, synthesis and biological evaluation of N-substituted nipecotamide derivatives as multifunctional agents for epilepsy treatment

European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 117613 - 117613

Published: April 1, 2025

Language: Английский

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Narrative Review on Common Traits of Parkinson’s Disease and Epilepsy

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(8), P. 2716 - 2716

Published: April 15, 2025

Epilepsy and Parkinson’s disease (PD) are two common neurological disorders, with a lifetime prevalence of approximately 1% 0.4%, respectively. Both conditions affect movement brain function were traditionally considered distinct, different pathophysiological mechanisms. However, recent research suggests potential links between them. Some studies indicate that epilepsy may contribute to the development PD due chronic neuroinflammation, excitotoxicity, neuronal loss. Conversely, PD-related neurodegeneration in dopaminergic pathways might increase susceptibility seizures. This article presents narrative review limited literature on mechanisms linking PD, including shared genetic factors, neurodegenerative processes, alterations neurotransmitter system. It also examines influence anti-seizure medications treatments symptoms progression both as well their clinical features. Additionally, limitations existing data this topic discussed. Understanding true relationship these disorders is crucial, it could provide insight into neurobiological lead improved therapeutic strategies.

Language: Английский

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Shooting an Arrow against Convulsion: Novel Triazole-Grafted Benzenesulfonamide Derivatives as Carbonic Anhydrase II and VII Inhibitors

Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

This study investigates new anticonvulsant substances that target the epilepsy-associated carbonic anhydrase isoforms II and VII. The 1,2,3-triazole with a benzenesulfonamide motif is present in produced molecules. Of these, 5b 5c exhibited remarkable selectivity inhibitory efficacy toward hCA VII over I. KI values of were 6.3 10.1 nM, respectively, 21.6 18.9 respectively. In pilocarpine-induced paradigm, vivo assessments showed decreased seizure severity susceptibility delayed onset diminished intensity. quick absorption stability demonstrated by pharmacokinetic investigations. Evaluations toxicity no neurotoxic effects high safety margin (LD50 > 2000 mg/kg). Mechanistic research has shown effectiveness maintaining neuronal integrity, reducing mTOR activation, raising hippocampus KCC2 levels. Compound 5b's binding interactions clarified docking dynamics experiments.

Language: Английский

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A Comprehensive Overview of the Current Status and Advancements in Various Treatment Strategies against Epilepsy

ACS Pharmacology & Translational Science, Journal Year: 2024, Volume and Issue: 7(12), P. 3729 - 3757

Published: Nov. 1, 2024

Epilepsy affects more than 70 million individuals of all ages worldwide and remains one the most severe chronic noncommunicable neurological diseases globally. Several neurotransmitters, membrane protein channels, receptors, enzymes, and, recently noted, various pathways, such as inflammatory mTORC complexes, play significant roles in initiation propagation seizures. Over past two decades, developments have been made diagnosis treatment epilepsy. Various pharmacological drugs with diverse mechanisms action other options developed to control seizures treat These include surgical treatment, nanomedicine, gene therapy, natural products, nervous stimulation, a ketogenic diet, gut microbiota, etc., which are developmental stages. Despite plethora options, one-third affected resistant current medications, while majority approved side effects, changes can occur, pharmacoresistance, effects on cognition, long-term problems, drug interactions, risks poor adherence, specific for certain psychological complications. Therefore, development new that no or minimal adverse is needed combat this deadly disease. In Review, we comprehensively summarize explain stages epilepsy well their status clinical trials advancements.

Language: Английский

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Relationship between inflammation/immunity and epilepsy: A multi-omics mendelian randomization study integrating GWAS, eQTL, and mQTL data

Epilepsy & Behavior, Journal Year: 2024, Volume and Issue: 161, P. 110112 - 110112

Published: Oct. 29, 2024

Language: Английский

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Understanding the role of TNFR2 signaling in the tumor microenvironment of breast cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: Nov. 28, 2024

Abstract Breast cancer (BC) is the most frequently diagnosed malignancy among women. It characterized by a high level of heterogeneity that emerges from interaction several cellular and soluble components in tumor microenvironment (TME), such as cytokines, cells tumor-associated immune cells. Tumor necrosis factor (TNF) receptor 2 (TNFR2) appears to play significant role microenvironmental regulation, progression, evasion, drug resistance, metastasis many types cancer, including BC. However, significance TNFR2 BC biology not fully understood. This review provides an overview biology, detailing its activation interactions with important signaling pathways TME (e.g., NF-κB, MAPK, PI3K/Akt pathways). We discuss potential therapeutic strategies targeting TNFR2, aim enhancing antitumor response insights into major checkpoint for future treatment patients

Language: Английский

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Drug arrows in the quiver-antiseizure, antiepileptic and neuroprotective medication: treatment and future aspects. A Focused Review

Seizure, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 1, 2024

Language: Английский

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A self-supervised graph network with time-varying functional connectivity for seizure prediction

Biomedical Signal Processing and Control, Journal Year: 2024, Volume and Issue: 102, P. 107375 - 107375

Published: Dec. 24, 2024

Language: Английский

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