Targeted Therapies for Epilepsy

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (20 February 2025) | Viewed by 6618

Special Issue Editors


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Guest Editor
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy
Interests: epileptogenesis; epilepsy; pharmacoresistance; status epilepticus

E-Mail Website
Guest Editor
Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, 41100 Modena, Italy
Interests: neurodegenerative disease; epilepsy; pharmacology; neuroinflammation
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Special Issue Information

Dear Colleagues,

Epilepsy is a major neurological disorder resulting in important health, social, and economic burdens for patients, families, and society. The most challenging issue in epilepsy research is the development of treatments able to prevent the appearance of spontaneous recurrent seizures after an initial precipitating injury, i.e., to prevent epileptogenesis. Indeed, the prevention of epileptogenesis should be the next-generation goal standard of new epilepsy treatments.

However, when epilepsy is already established, new antiseizure medications (ASMs) may also be suitable. Indeed, despite the availability of various ASMs, one-third of patients suffering from epilepsy are considered “drug-resistant” and cannot achieve satisfactory seizure control. In this case, a major obstacle in developing new targeted therapies for epilepsy, and especially drug-resistant epilepsy, is that the mechanisms of drug resistance are still scarcely understood. In addition to this, most patients with chronic intractable epilepsy are resistant to different mechanistically distinct anti-seizure medications.

Another important goal for a new targeted therapy for epilepsy should be to avoid the adverse effects of ASMs, which normally result in drug discontinuation.

For these reasons, new chemical compounds, and alternative potential therapies such as neurostimulation, dietary treatments, gene therapy, and cell transplantation, can be proposed to control epilepsy.

Prof. Dr. Giuseppe Biagini
Dr. Anna-Maria Costa
Dr. Chiara Lucchi
Guest Editors

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Keywords

  • epilepsy
  • temporal lobe epilepsy
  • neurological disorder
  • spontaneous recurrent seizures
  • epileptogenesis
  • antiepileptogenic medications
  • antiseizure medications
  • drug-resistant epilepsy
  • adverse effects
  • drug discontinuation

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Published Papers (3 papers)

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Research

19 pages, 6033 KiB  
Article
Anti-Epileptic Activity of Mitocurcumin in a Zebrafish–Pentylenetetrazole (PTZ) Epilepsy Model
by Alin Dumitru Ciubotaru, Carmen-Ecaterina Leferman, Bogdan-Emilian Ignat, Anton Knieling, Delia Lidia Salaru, Dana Mihaela Turliuc, Liliana Georgeta Foia, Lorena Dima, Bogdan Minea, Luminita Diana Hritcu, Bogdan Ionel Cioroiu, Laura Stoica, Ioan-Adrian Ciureanu, Alin Stelian Ciobica, Bogdan Alexandru Stoica and Cristina Mihaela Ghiciuc
Pharmaceuticals 2024, 17(12), 1611; https://doi.org/10.3390/ph17121611 - 29 Nov 2024
Cited by 1 | Viewed by 1531
Abstract
Background/Objectives: Ongoing challenges in epilepsy therapy warrant research on alternative treatments that offer improved efficacy and reduced side effects. Designed to enhance mitochondrial targeting and increase bioavailability, mitocurcumin (MitoCur) was evaluated for the first time as an antiepileptic agent, with curcumin (Cur) [...] Read more.
Background/Objectives: Ongoing challenges in epilepsy therapy warrant research on alternative treatments that offer improved efficacy and reduced side effects. Designed to enhance mitochondrial targeting and increase bioavailability, mitocurcumin (MitoCur) was evaluated for the first time as an antiepileptic agent, with curcumin (Cur) and sodium valproate (VPA), a standard antiepileptic drug, included for comparison. This study investigated the effects on seizure onset, severity, and progression in a zebrafish model of pentylenetetrazole (PTZ)-induced seizures and measured the concentrations of the compounds in brain tissue. Methods: Zebrafish were pre-treated with MitoCur and Cur (both at 0.25 and 0.5 µM doses) and VPA (0.25 and 0.5 mM) and observed for four minutes to establish baseline locomotor behavior. Subsequently, the animals were exposed to a 5 mM PTZ solution for 10 min, during which seizure progression was observed and scored as follows: 1—increased swimming; 2—burst swimming, left and right movements; 3—circular movements; 4—clonic seizure-like behavior; 5—loss of body posture. The studied compounds were quantified in brain tissue through HPLC and LC-MS. Results: Compared to the control group, all treatments reduced the distance moved and the average velocity, without significant differences between compounds or doses. During PTZ exposure, seizure latencies revealed that all treatments effectively delayed seizure onset up to score 4, demonstrating efficacy in managing moderate seizure activity. Notably, MitoCur also provided significant protection against the most severe seizure score (score 5). Brain tissue uptake analysis indicated that MitoCur achieved higher concentrations in the brain compared to Cur, at both doses. Conclusions: These results highlight the potential of MitoCur as a candidate for seizure management. Full article
(This article belongs to the Special Issue Targeted Therapies for Epilepsy)
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10 pages, 1121 KiB  
Article
Subthreshold Cannabidiol Potentiates Levetiracetam in the Kainic Acid Model of Temporal Lobe Epilepsy: A Pilot Study
by Chiara Lucchi, Mattia Marcucci, Kawther Ameen Muhammed Saeed Aledresi, Anna-Maria Costa, Giuseppe Cannazza and Giuseppe Biagini
Pharmaceuticals 2024, 17(9), 1187; https://doi.org/10.3390/ph17091187 - 10 Sep 2024
Cited by 2 | Viewed by 1371
Abstract
Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered [...] Read more.
Refractoriness to antiseizure medications is still a major concern in the pharmacotherapy of epilepsy. For this reason, we decided to evaluate the combination of levetiracetam and cannabidiol, administered at a subthreshold dose, to limit the possible adverse effects of this phytocannabinoid. We administered levetiracetam (300 mg/kg/day, via osmotic minipumps), cannabidiol (120 mg/kg/day, injected once a day subcutaneously), or their combination for one week in epileptic rats. Saline-treated epileptic rats were the control group. Animals were monitored with video electroencephalography the week before and after the treatment. No changes were found in the controls. Levetiracetam did not significantly reduce the total seizure number or the overall seizure duration. Still, the overall number of seizures (p < 0.001, Duncan’s new multiple range test) and their total duration (p < 0.01) increased in the week following treatment withdrawal. Cannabidiol did not change seizures when administered as a single drug. Instead, levetiracetam combined with cannabidiol resulted in a significant reduction in the overall number and duration of seizures (p < 0.05), when comparing values measured during treatment with both pre- and post-treatment values. These findings depended on changes in convulsive seizures, while non-convulsive seizures were stable. These results suggest that cannabidiol determined a remarkable potentiation of levetiracetam antiseizure effects at a subthreshold dose. Full article
(This article belongs to the Special Issue Targeted Therapies for Epilepsy)
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12 pages, 594 KiB  
Article
Efficacy of Perampanel in Refractory and Super-Refractory Status Epilepticus with Suspected Inflammatory Etiology: A Case Series
by Annacarmen Nilo, Alberto Vogrig, Marco Belluzzo, Christian Lettieri, Lorenzo Verriello, Mariarosaria Valente and Giada Pauletto
Pharmaceuticals 2024, 17(1), 28; https://doi.org/10.3390/ph17010028 - 24 Dec 2023
Cited by 2 | Viewed by 2922
Abstract
(1) Background: Increasing evidence supports the anti-inflammatory and neuroprotective role of perampanel (PER), mediated by decreased expression of pro-inflammatory cytokines and by interference with apoptosis processes. Therefore, the use of PER to treat status epilepticus (SE) with suspected inflammatory etiology is appealing and [...] Read more.
(1) Background: Increasing evidence supports the anti-inflammatory and neuroprotective role of perampanel (PER), mediated by decreased expression of pro-inflammatory cytokines and by interference with apoptosis processes. Therefore, the use of PER to treat status epilepticus (SE) with suspected inflammatory etiology is appealing and deserves further investigation. (2) Methods: We retrospectively analyzed seven patients (five F, two M; median age: 62 years) with refractory and super-refractory SE due to a probable or defined inflammatory etiology and treated with PER. (3) Results: PER was administered as the third (4/7) or fourth drug (3/7), with a median loading dose of 32 mg/day (range: 16–36 mg/day) and a median maintenance dose of 10 mg/day (range: 4–12 mg/day). In five cases, SE was focal, while in two patients, it was generalized. SE was caused by systemic inflammation in three patients, while in the other four subjects, it was recognized to have an autoimmune etiology. SE resolution was observed after PER administration in all cases, particularly within 24 h in the majority of patients (4/7, 57.1%). (4) Conclusions: Our data support the efficacy of PER in treating SE when first- and second-line ASMs have failed and suggest a possible earlier use in SE cases that are due to inflammatory/autoimmune etiology. Full article
(This article belongs to the Special Issue Targeted Therapies for Epilepsy)
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