Pharmacological approaches in drug-resistant pediatric epilepsies caused by pathogenic variants in potassium channel genes

Frontiers in Cellular Neuroscience, Год журнала: 2025, Номер 18

Опубликована: Янв. 24, 2025

Variants in genes encoding for voltage-gated K + (Kv) channels are frequent cause of drug-resistant pediatric epilepsies. Obtaining a molecular diagnosis gives the opportunity to assess efficacy pharmacological strategies based on vitro features mutant channels. In this retrospective observational study, we selected patients with epilepsies caused by variants potassium channel genes, followed at Fondazione IRCCS Istituto Neurologico Carlo Besta Milan, Italy. After experimental characterization variants’ functional properties transiently transfected Chinese Hamster Ovary (CHO) cells, identified drugs be used as approaches. We recruited six carrying different missense four Kv (Kv7.2, Kv7.3, Kv3.1, and Na 1.1). experiments demonstrated that Kv7 induced loss-of-function (LoF) effects, while those affecting Kv3.1 or 1.1 led gain-of-function (GoF). Moreover, found activator gabapentin was able revert LoF effects Kv7.2/Kv7.3 variants, channel-blocker fluoxetine counteracted GoF variants. According data, were treated gabapentin. While treatment resulted successful two (#1, Kv7.2 G310S variant; #3, Kv7.3 V359L D542N), it detrimental remaining case (#2, D535E), requiring drug withdrawal. The application vivo counteract determined significant reduction both seizure frequency behavior disturbances patient #4 (Kv3.1 V425M), subjects (#5, S937G #6, R262Q). However, latter case, halted due severe behavioral side effects. For most herein reported, strategies, according Kv-channels pathogenic improvement epileptic cognitive features.

Язык: Английский

Remote-Controlled Wireless Bioelectronics for Fluoxetine Therapy to Promote Wound Healing in a Porcine Model

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 21, 2024

Abstract Wound healing presents a significant challenge in biomedical science, requiring precise therapeutic delivery and real-time monitoring. Bioelectronic systems offer promising solution but remain largely unexplored for wound care, particularly large animal models that reflect human dynamics. This study introduces remote controlled wireless bioelectronic platform equipped with an iontophoretic pump to deliver fluoxetine, selective serotonin reuptake inhibitor promotes repair. In vitro ex-vivo testing validated efficient on demand fluoxetine delivery. vivo experiments porcine model demonstrated clear efficacy over 3-day 7-day periods. The system enhanced outcomes, increasing re-epithelialization by 37% (H&E staining), reducing the M1/M2 macrophage ratio 33%, stimulating neuronal growth at site. delivers controlled, remotely-controlled manner while allowing direct imaging can be used monitor progress. Additionally, it allows dose temporal of treatment enhance outcome future studies.

Язык: Английский

Fluoxetine promotes the recovery of dysphagia and improves nutritional status and neurotrophic status in dysphagia patients after acute ischemic stroke

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 2, 2024

Язык: Английский