Article
Clinical Neurology
Sophie F. Hill, Julie M. Ziobro, Paymaan Jafar-Nejad, Frank Rigo, Miriam H. Meisler
Summary: Voltage-gated sodium and potassium channels play a crucial role in regulating neuronal action potentials, and mutations in these channels can lead to seizure disorders. This study demonstrates that reducing the expression of Scn8a can compensate for loss-of-function mutations in Kcna1 and Kcnq2, providing a potential therapeutic approach for genetic epilepsies caused by mutations in potassium channel genes.
Article
Clinical Neurology
Devon Knight, Sonal Mahida, Mckenna Kelly, Annapurna Poduri, Heather E. Olson
Summary: Retrospective review of eight patients with KCNQ2-related developmental and epileptic encephalopathy (DEE) treated with ezogabine showed that the medication effectively reduced seizures and improved development with minimal side effects. Weaning from ezogabine was associated with increased seizures and behavioral disturbances in some patients. These findings support the use of ezogabine in KCNQ2-related DEE.
Article
Cell Biology
Xiaoxiao Li, Qiansen Zhang, Peipei Guo, Jie Fu, Lianghe Mei, Dashuai Lv, Jiangqin Wang, Dongwu Lai, Sheng Ye, Huaiyu Yang, Jiangtao Guo
Summary: Cryo-EM structures of human KCNQ2 in apo state and in complex with two activators, zzt240 or retigabine, reveal different ligand recognition and activation mechanisms, providing a structural basis for drug optimization and design.
Review
Developmental Biology
Kristen Springer, Nissi Varghese, Anastasios V. Tzingounis
Summary: KCNQ2 and KCNQ3 channel variants are associated with a spectrum of developmentally regulated diseases and are potential targets for new antiepileptic drugs. The current understanding is that they assemble as heteromeric channels, but research suggests that channel composition in the nervous system may be dynamic and flexible, requiring a more flexible view for a comprehensive understanding of KCNQ2 and KCNQ3 channelopathies.
DEVELOPMENTAL NEUROSCIENCE
(2021)
Article
Multidisciplinary Sciences
Heun Soh, Kristen Springer, Klarita Doci, Jeremy L. Balsbaugh, Anastasios V. Tzingounis
Summary: KCNQ2 and KCNQ3 channels are associated with neurodevelopmental disorders and are therapeutic targets for neurological and neuropsychiatric diseases. The study reveals that KCNQ2/5 tandems can form functional channels independently of KCNQ3 and KCNQ2 associates with KCNQ5 in the brain even without KCNQ3. This suggests that the composition of KCNQ channels is more diverse than previously recognized.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Neurosciences
Tiantian Xiao, Xiang Chen, Yan Xu, Huiyao Chen, Xinran Dong, Lin Yang, Bingbing Wu, Liping Chen, Long Li, Deyi Zhuang, Dongmei Chen, Yuanfeng Zhou, Huijun Wang, Wenhao Zhou
Summary: Patients with novel KCNQ2 variants exhibit variable phenotypes, with some experiencing early neonatal seizures and others showing signs of neurodevelopmental delay. On the other hand, patients with 20q13.3 deletions tend to have normal neurological development.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Neurosciences
Tracy S. Gertler, Suraj Cherian, Jean-Marc Dekeyser, Jennifer A. Kearney, Alfred L. George
Summary: Pathogenic variants in KCNT1 gene are associated with intractable epilepsy and may drive the development of epilepsy through alterations in inhibitory signaling and neuronal excitability.
NEUROBIOLOGY OF DISEASE
(2022)
Article
Clinical Neurology
Nina E. Ottosson, Malin Silvera Ejneby, Xiongyu Wu, Argel Estrada-Mondragon, Michelle Nilsson, Urban Karlsson, Melanie Schupp, Salome Rognant, Thomas Andrew Jepps, Peter Konradsson, Fredrik Elinder
Summary: Resin acid derivatives have been found to activate the hK(V)7.2/7.3 channel, showing potential for epilepsy treatment and demonstrating significant antiseizure effects in animal studies. These compounds act on the channel in a unique way compared to existing drugs, and have fewer side effects.
Article
Medicine, Research & Experimental
Carlos G. Vanoye, Reshma R. Desai, Zhigang Ji, Sneha Adusumilli, Nirvani Jairam, Nora Ghabra, Nishtha Joshi, Eryn Fitch, Katherine L. Helbig, Dianalee McKnight, Amanda S. Lindy, Fanggeng Zou, Ingo Helbig, Edward C. Cooper, Alfred L. George
Summary: This study investigated the functional and pharmacological properties of numerous KCNQ2 gene variants using automated patch clamp recordings. The results showed that most disease-associated KCNQ2 variants exhibited prominent loss-of-function with dominant-negative effects, providing strong evidence for their pathogenicity. Additionally, the response of KCNQ2 variants to retigabine, a proposed precision therapy, varied depending on the genotype.
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)
Review
Pharmacology & Pharmacy
Valentin K. Gribkoff, Raymond J. Winquist
Summary: Several mutations to members of CNS potassium channel families are associated with rare forms of neonatal onset epilepsy or syndromes with epilepsy characteristics. These mutations significantly increase the probability of generalized seizure disorders and can result in more severe developmental syndromes. Efforts to target these syndromes through pharmacological or genetic modulation have been made.
BIOCHEMICAL PHARMACOLOGY
(2023)
Article
Genetics & Heredity
Stephanie Boets, Katrine M. Johannesen, Anne Destree, Filippo Manti, Georgia Ramantani, Gaetan Lesca, Laurent Vercueil, Mary Kay Koenig, Pasquale Striano, Rikke Steensbjerre Moller, Edward Cooper, Sarah Weckhuysen
Summary: Research shows that the frequency of seizures in KCNQ2 encephalopathy patients decreases over time, with most patients being seizure-free in adulthood. Patients commonly experience intellectual disability, motor issues, language difficulties, and behavioral problems that require ongoing attention.
JOURNAL OF MEDICAL GENETICS
(2022)
Article
Clinical Neurology
Robertino Dilena, Eleonora Mauri, Alessio Di Fonzo, Cristina Bana, Paola Francesca Ajmone, Claudia Rigamonti, Tamara Catenio, Silvana Gangi, Pasquale Striano, Monica Fumagalli
Summary: We reported a family case of neonatal-onset KCNQ2-related epilepsy caused by a novel intronic mutation and discussed the laboratory studies performed on this mutation.
FRONTIERS IN NEUROLOGY
(2022)
Article
Neurosciences
Juan Pablo Lopez, Malte D. Luecken, Elena Brivio, Stoyo Karamihalev, Aron Kos, Carlo De Donno, Asaf Benjamin, Huanqing Yang, Alec L. W. Dick, Rainer Stoffel, Cornelia Flachskamm, Andrea Ressle, Simone Roeh, Rosa-Eva Huettl, Andrea Parl, Carola Eggert, Bozidar Novak, Yu Yan, Karin Yeoh, Maria Holzapfel, Barbara Hauger, Daniela Harbich, Bianca Schmid, Rossella Di Giaimo, Christoph W. Turck, Mathias Schmidt, Jan M. Deussing, Matthias Eder, Julien Dine, Fabian J. Theis, Alon Chen
Summary: This study identifies the molecular mechanisms responsible for the sustained antidepressant effects of ketamine and highlights the role of the Kcnq2 gene in this process. It also demonstrates the ketamine-specific effects that can be augmented by adjunctive treatment with a KCNQ activator, providing important insights for clinical implications.
Article
Genetics & Heredity
Randi von Wrede, Monika Jeub, Idil Arioez, Christian E. Elger, Hubertus von Voss, Hanns-Georg Klein, Albert J. Becker, Susanne Schoch, Rainer Surges, Wolfram S. Kunz
Summary: This study describes four patients with different types of epilepsy-related disorders, all carrying novel KCNH1 mutations. The findings suggest that these mutations may lead to severe phenotypes, with one family showing a weaker association. The case series expands the phenotypic spectrum of KCNH1-associated diseases through genetic analysis.
