Article
Pharmacology & Pharmacy
Lindsey Shapiro, Andrew Escayg, Jennifer C. Wong
Summary: Voltage-gated sodium channel genes are important for human epilepsy. SCN8A mutations can cause various clinical symptoms, including different types of seizures, movement disorders, intellectual disabilities, and autism. CBD treatment in RL/+ mutant mice showed dose-dependent seizure resistance and improved social behavior and reduced hyperactivity. CBD may be beneficial for patients with SCN8A-associated disease.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Jennifer C. Wong, Kameryn M. Butler, Lindsey Shapiro, Jacquelyn T. Thelin, Kari A. Mattison, Kathryn B. Garber, Paula C. Goldenberg, Shobana Kubendran, G. Bradley Schaefer, Andrew Escayg
Summary: SCN8A mutations, mainly de novo missense variants, are associated with epileptic encephalopathy. Mouse models with overlapping in-frame deletions in the voltage sensor region of domain 4 exhibit increased seizure susceptibility. Clinical relevance of mutations is highlighted by identification of patients with the same SCN8A deletion.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Neurosciences
Eric R. Wengert, Raquel M. Miralles, Kyle C. A. Wedgwood, Pravin K. Wagley, Samantha M. Strohm, Payal S. Panchal, Abrar Majidi Idrissi, Ian C. Wenker, Jeremy A. Thompson, Ronald P. Gaykema, Manoj K. Patel
Summary: SCN8A epileptic encephalopathy is a devastating epilepsy syndrome caused by mutant SCN8A gene encoding NaV1.6 channel, with inhibitory interneurons playing a critical role in seizure generation through hyperexcitability and sensitivity to action potential failure. Aberrantly large persistent sodium currents directly contribute to abnormal physiology in SST interneurons.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Clinical Neurology
Simona Lattanzi, Michele Ascoli, Laura Canafoglia, Maria Paola Canevini, Sara Casciato, Emanuele Cerulli Irelli, Valentina Chiesa, Filippo Dainese, Giovanni De Maria, Giuseppe Didato, Giancarlo Di Gennaro, Giovanni Falcicchio, Martina Fanella, Massimo Gangitano, Angela La Neve, Oriano Mecarelli, Elisa Montalenti, Alessandra Morano, Federico Piazza, Chiara Pizzanelli, Patrizia Pulitano, Federica Ranzato, Eleonora Rosati, Laura Tassi, Carlo Di Bonaventura
Summary: This study assessed the sustained reduction in seizure frequency with adjunctive brivaracetam (BRV) in real-world practice for patients with epilepsy. The results showed that BRV was associated with sustained seizure frequency reduction from the first day of treatment in a subset of patients with uncontrolled focal epilepsy.
Article
Neurosciences
Sophie F. Hill, Paymaan Jafar-Nejad, Frank Rigo, Miriam H. Meisler
Summary: Reducing expression of the potassium channel gene Kcnt1 appears to be a potential therapeutic target for treating SCN1A and SCN8A epilepsy, as it prolongs the survival of mice with mutations in these sodium channel genes.
FRONTIERS IN NEUROSCIENCE
(2023)
Article
Clinical Neurology
Sara Matricardi, Sandrine Cestele, Marina Trivisano, Benedetta Kassabian, Nathalie Leroudier, Roberta Vittorini, Margherita Nosadini, Elisabetta Cesaroni, Sabrina Siliquini, Cristina Marinaccio, Francesca Longaretti, Barbara Podesta, Francesca Felicia Operto, Concetta Luisi, Stefano Sartori, Clementina Boniver, Nicola Specchio, Federico Vigevano, Carla Marini, Massimo Mantegazza
Summary: This study aimed to refine the spectrum of SCN1A epileptic disorders beyond DS and GEFS+ and optimize antiseizure management. Nine of the 16 probands had de novo pathogenic variants causing DEE, while seven probands manifested focal epilepsies with mild or no intellectual disability. Sodium channel blockers never worsened seizures, and functional analysis showed a gain of channel function for three representative variants. The study highlights the wide range of SCN1A disorders and the importance of SCN1A testing in pediatric, familial and nonfamilial, focal epilepsies.
Review
Biochemistry & Molecular Biology
Tsang-Shan Chen, Ming-Chi Lai, Huai-Ying Ingrid Huang, Sheng-Nan Wu, Chin-Wei Huang
Summary: Epilepsy is a common chronic neurological disorder in modern society. The immunological factors and the interaction between ion channels and the immune system play important roles in the development and progression of epilepsy. Recognizing immune-mediated epilepsy and understanding the pathophysiology are crucial for early intervention and effective treatment.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Alvaro Beltran-Corbellini, Maria Romeral-Jimenez, Pablo Mayo, Irene Sanchez-Miranda Roman, Pablo Iruzubieta, Juan Luis Chico-Garcia, Paloma Parra-Diaz, Irene Garcia-Morales, Rafael Toledano, Angel Aledo-Serrano, Antonio Gil-Nagel
Summary: The purpose of this study was to determine the effectiveness and safety of cenobamate in patients with highly refractory focal epilepsy. The results showed that cenobamate significantly reduced seizure frequency and intensity, with a manageable safety profile.
SEIZURE-EUROPEAN JOURNAL OF EPILEPSY
(2023)
Article
Multidisciplinary Sciences
Ping Dong, Yang Zhang, Arsen S. Hunanyan, Mohamad A. Mikati, Jianmin Cui, Huanghe Yang
Summary: An increasing number of gain-of-function BK channelopathies have been found to be associated with motor deficits and dyskinesia-like behaviors. Our study reveals the neuronal mechanism of BK gain-of-function in absence epilepsy and dyskinesia, and suggests that BK inhibition is a promising therapeutic strategy for BK gain-of-function-induced neurological disorders.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Alexa Joanna Roemmich, Thy Vu, Tamas Lukacsovich, Charlesice Hawkins, Soleil S. Schutte, Diane K. O'Dowd
Summary: Mutations in the voltage-gated sodium channel gene SCN1A are associated with human epilepsy disorders. This study found that Drosophila lines with R-C or R-H mutations showed reduced lifespan and seizures, while electrophysiological recordings revealed sustained neuronal depolarizations and altered firing frequency. The only significant change observed in sodium currents was a hyperpolarized deactivation threshold in R-C and R-H mutants.
Article
Computer Science, Information Systems
Omaima Ouichka, Amira Echtioui, Habib Hamam
Summary: This article proposes a method based on deep learning models to automatically predict epileptic seizures. The experimental results show that the methods based on 3-CNN and 4-CNN achieve the best accuracy values of 95%.
Review
Geriatrics & Gerontology
Yilin Wang, Penghu Wei, Feng Yan, Yumin Luo, Guoguang Zhao
Summary: Epilepsy is a serious neurological disorder that can cause brain damage, and animal models help understand the mechanisms of epilepsy and select treatment drugs.
Review
Clinical Neurology
Taha Gul Shaikh, Syeda Fatima Saba Hasan, Hiba Ahmed, Amal Iqbal Kazi, Ruhma Mansoor
Summary: Epilepsy is a chronic brain disease affecting millions of people worldwide. While anti-seizure drugs are commonly used, they fail to be effective in about one third of patients. This has led to the exploration of new treatments, such as angiotensin receptor blockers (ARBs), in reducing neuronal over-excitation in epilepsy. A review of existing literature suggests that ARBs have a high potential in treating epilepsy, particularly in patients who are unresponsive to conventional treatment options. However, further human-based trials are needed to draw definitive conclusions, and monitoring for adverse effects is crucial when using ARBs in epilepsy patients.
NEUROLOGICAL SCIENCES
(2023)
Article
Clinical Neurology
Gareth Morris, Mona Heiland, Kai Lamottke, Haifeng Guan, Thomas D. M. Hill, Yijun Zhou, Qianjin Zhu, Stephanie Schorge, David C. Henshall
Summary: Drug-resistant epilepsy is still a major clinical and societal burden. This study evaluated the potential of BICS01, a synthetic compound, as a new anti-seizure drug. The results showed that BICS01 rapidly reduced the frequency of epileptiform bursting without affecting network excitability or short-term synaptic facilitation. It was well tolerated at high doses in animal models. However, it did not have a protective effect against acute seizures. Further studies are needed to improve its pharmacokinetics, brain accumulation, and understand its mechanism of action.
FRONTIERS IN NEUROLOGY
(2022)
Review
Pharmacology & Pharmacy
Siddesh Kelkar, Namrata Nailwal, Nirav Yogesh Bhatia, Gaurav Doshi, Sadhana Sathaye, Angel Pavalu Godad
Summary: Inflammation is a mechanism of the body to activate the immune system and prevent bacteria and viruses from causing toxic effects. Voltage-gated ion channel blockers can be an important alternative to deal with the side effects of current drugs.
CURRENT DRUG TARGETS
(2022)
Article
Biochemistry & Molecular Biology
Alessio Malacrida, Mirko Rivara, Alessandro Di Domizio, Giacomo Cislaghi, Mariarosaria Miloso, Valentina Zuliani, Gabriella Nicolini
BIOORGANIC & MEDICINAL CHEMISTRY
(2020)
Article
Multidisciplinary Sciences
Wout J. Weuring, Sakshi Singh, Linda Volkers, Martin B. Rook, Ruben H. van't Slot, Marjolein Bosma, Marco Inserra, Irina Vetter, Nanda M. Verhoeven-Duif, Kees P. J. Braun, Mirko Rivara, Bobby P. C. Koeleman
Article
Chemistry, Organic
Saurabh K. Tiwari, Km Neha Shivhare, Manoj K. Patel, Vikas Yadav, Mohd Nazeef, I. R. Siddiqui
Summary: We report an eco-friendly and facile strategy for the synthesis of 1,4-dihydropyridine (1,4-DHP) derivatives through a one pot multi-component Hantzsch reaction using glycerol as a promoting medium. The protocol offers a greener, economical, and expeditious synthesis of biologically significant 1,4-DHPs with moderate to excellent yields under metal-free mild reaction conditions. The additional advantages include operational simplicity, cost effectiveness, and reusability with the avoidance of hazardous volatile solvents.
POLYCYCLIC AROMATIC COMPOUNDS
(2022)
Article
Chemistry, Multidisciplinary
Manjula Singh, Laxmi Kant Sharma, Rahul Dubey, Manoj Kumar Patel, Ved Prakash, Rana Krishna Pal Singh
Review
Clinical Neurology
Eric R. Wengert, Manoj K. Patel
Summary: Voltage-gated sodium channels play a crucial role in generating action potentials in the nervous system, with a persistent sodium current contributing to normal neuronal function but potentially playing a pathogenic role in epilepsy. Targeting the persistent sodium current may hold promise for developing novel anti-seizure medication strategies.
Article
Clinical Neurology
Ian C. Wenker, Frida A. Teran, Eric R. Wengert, Pravin K. Wagley, Payal S. Panchal, Elizabeth A. Blizzard, Priyanka Saraf, Jacy L. Wagnon, Howard P. Goodkin, Miriam H. Meisler, George B. Richerson, Manoj K. Patel
Summary: The study revealed that apnea coincident with the tonic phase of a seizure, and subsequent failure to resume breathing, are determining events that cause seizure-induced death in Scn8a mutant mice.
ANNALS OF NEUROLOGY
(2021)
Article
Neurosciences
Eric R. Wengert, Ian C. Wenker, Elizabeth L. Wagner, Pravin K. Wagley, Ronald P. Gaykema, Jung-Bum Shin, Manoj K. Patel
Summary: This study demonstrates that mice harboring an Scn8a allele with a patient-derived mutation are susceptible to audiogenic seizures and seizure-induced death, providing a new model for studying seizure-induced death. Activation of adrenergic receptors is necessary and sufficient for recovery of breathing and prevention of seizure-induced death in this novel audiogenic seizure-induced death model.
FRONTIERS IN NEUROSCIENCE
(2021)
Editorial Material
Clinical Neurology
Eric R. Wengert, Manoj K. Patel
Article
Pharmacology & Pharmacy
Ankita Sharma, Shardulya Shukla, Abul Quasim, Manoj Kumar Patel, Raj Kumar, Om Prakash Chaurasia, Shweta Saxena
Summary: This study developed an in vitro regeneration protocol for Rubia cordifolia using nodal and leaf explants, and compared the phytochemical profiles of in vitro grown leaves (RUML) and roots (RUMR). The results showed that both leaves and roots contain medicinal compounds, with 8 compounds commonly present in both extracts.
ANNALS OF PHYTOMEDICINE-AN INTERNATIONAL JOURNAL
(2021)
Article
Biology
Alessio Malacrida, Alessandro Di Domizio, Angela Bentivegna, Giacomo Cislaghi, Eleonora Messuti, Silvia Maria Tabano, Carlo Giussani, Valentina Zuliani, Mirko Rivara, Gabriella Nicolini
Summary: Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis. Surgical resection followed by radiotherapy and temozolomide (TMZ) treatment represents the standard strategy for GBM. However, tumor recurrences and TMZ resistance are common, requiring the development of new pharmacological strategies. This study discovered that MV1035, an imidazobenzoxazin-5-thione, can reduce migration and invasiveness of GBM cells and has a synergistic effect when used in combination with TMZ.
Article
Biochemistry & Molecular Biology
Michele Massa, Mirko Rivara, Gaetano Donofrio, Luigi Cristofolini, Erica Peracchia, Carlotta Compari, Franco Bacciottini, Davide Orsi, Valentina Franceschi, Emilia Fisicaro
Summary: This paper evaluates the gene delivery ability of newly synthesized gemini bis-pyridinium surfactants and compares them with compounds of different lengths. The results suggest that these surfactants could be a valuable tool for gene delivery purposes, but their performance depends on the spacer length and structure in solution.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Chemistry, Medicinal
Linda Benincasa, Eleonora Molesti, Alessandro Manenti, Emanuele Montomoli, Alessio Malacrida, Valentina Zuliani, Mirko Rivara, Gabriella Nicolini, Alessandro Di Domizio
Summary: ALKBH5 inhibitors can reduce the replication of SARS-CoV-2 through an interaction with host cells, potentially providing a new strategy for antiviral treatment. This finding paves the way for the development of molecules that are less susceptible to drug resistance.
LETTERS IN DRUG DESIGN & DISCOVERY
(2023)
Article
Engineering, Electrical & Electronic
Aarti Chauhan, Manoj Kumar Patel, Shilpa Chaudhary, Manoj Kumar Nayak, Surender Singh Saini, Pratap Pullammanappallil, Nadarajah Manivannan, Geoffrey Robert Mitchell, Wamadeva Balachandran
Summary: This research aims to evaluate the chargeability of sodium hypochlorite and an air-assisted electrostatic disinfection device. Five different surfaces were examined to assess efficacy, survival time, off-target losses, spray coverage, and disinfectant consumption. The results showed that sodium hypochlorite achieved a significant charge-to-mass ratio of 2.43 mC/kg at specific conditions and effectively eliminated Pseudomonas aeruginosa, Clostridium perfringens, and Bacteriophage MS2 colonies at a concentration of 1000 mg/L.
JOURNAL OF ELECTROSTATICS
(2023)
Article
Biochemistry & Molecular Biology
Michele Massa, Mirko Rivara, Thelma A. Pertinhez, Carlotta Compari, Gaetano Donofrio, Luigi Cristofolini, Davide Orsi, Valentina Franceschi, Emilia Fisicaro
Summary: The development of efficient and safe non-viral vectors is crucial for gene-based medicine. This study shows that the length of the hydrophobic chain does not significantly affect gene delivery, while the length of the spacer plays a key role in gene transfer capacity.
Article
Multidisciplinary Sciences
Aarti Chauhan, Manoj Kumar Patel, Manoj Kumar Nayak, Surender Singh Saini
Summary: Electrostatic spraying is an effective method for disinfecting surfaces to prevent transmission of SARS-CoV-2. The design and performance of a motorized pressure-nozzle based handheld electrostatic disinfection device were optimized, and the chargeability of various disinfectants was investigated.