Therapeutic Potential of Sodium Channel Blockers as a Targeted Therapy Approach in KCNA1-Associated Episodic Ataxia and a Comprehensive Review of the Literature

Autor: Stephan Lauxmann, Lukas Sonnenberg, Nils A. Koch, Christian Bosselmann, Natalie Winter, Niklas Schwarz, Thomas V. Wuttke, Ulrike B. S. Hedrich, Yuanyuan Liu, Holger Lerche, Jan Benda, Josua Kegele

Publikováno v: Frontiers in Neurology, Vol 12 (2021)

Introduction: Among genetic paroxysmal movement disorders, variants in ion channel coding genes constitute a major subgroup. Loss-of-function (LOF) variants in KCNA1, the gene coding for KV1.1 channels, are associated with episodic ataxia type 1 (EA1

Externí odkaz: https://doaj.org/article/20e94abcd4a240c4ab74bc5d56dc90b3

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

Autor: Roseline Caume, M Scott Perry, Massimo Mastrangelo, Margarete Koch-Hogrebe, Pasquale Striano, Karen Müller-Schlüter, Petra Laššuthová, Monisa D. Wagner, Ingo Helbig, Stephan Lauxmann, Emmanuel Scalais, Marie-Cécile Nassogne, Silvia Masnada, Henrike O. Heyne, Konrad Platzer, Frederic Bilan, Chloe A Stutterd, Sonja Walsh, Katrine M Johannesen, Damien Lederer, Ngoc Minh Le, Christina Fenger, Daniel Tibussek, Lukas Sonnenberg, Andrea Berger, Yuanyuan Liu, Mikhail Abramov, Karen E. Wain, Sergey Korostelev, P Y Billie Au, Elena L. Dadali, An-Sofie Schoonjans, Cornelia Betzler, Artem Borovikov, Johanna Krüger, Maert Rannap, Sebastian Lebon, Nils A Koch, Nancy Eisenhauer, Judith Kroell-Seger, Julian Schubert, Marije Meuwissen, Caroline Lund, Mark Fitzgerald, Federico Zara, Siddharth Srivastava, Claudia M Bonardi, Pia Zacher, Haim Bassan, Arve Vøllo, Katherine B. Howell, Francesca Darra, Guido Rubboli, Stephen W. Scherer, Bénédicte Gérard, Stefano Sartori, Annapurna Poduri, Helene Verhelst, Katalin Sterbova, Mathilde Nizon, Marketa Vlckova, Christina E. Hoei-Hansen, Renzo Guerrini, Ilya V. Kanivets, Juliann M. Savatt, Johannes Rebstock, Jakob Christensen, Cecilia Altuzarra, Dennis Lal, Judith S. Verhoeven, Agathe Roubertie, Constanze Heine, Dagmar Wieczorek, Ingo Borggraefe, Aster V. E. Harder, Anne Destrée, Wen-Hann Tan, Tobias Brünger, Shoji Ichikawa, Laura Canafoglia, Mahmoud Koko, Sergey Kutsev, Sabine Grønborg, Patrizia Accorsi, Heather E. Olson, Bert van der Zwaag, Cathrine E Gjerulfsen, Patrick May, A. A. Sharkov, M. Mahdi Motazacker, Manuela Pendziwiat, Richard J. Leventer, Anna Jansen, Lucio Giordano, Holger Lerche, Carla Marini, Karl Martin Klein, Eva H. Brilstra, Ahmed Eltokhi, Ethan M. Goldberg, Walid Fazeli, Rikke S. Møller, Dorota Hoffman-Zacharska, Michael Alber, Susanne Ruf, Jennifer L. Howe, Phillis Lakeman, Josua Kegele, Katherine L. Helbig, Marga Buzatu, Alice W Ho, Jan Benda, Ilona Krey, Marion Gérard, Sara Matricardi, Thomas U. Mayer, Philippe Gelisse, Jong M. Rho, Johannes R. Lemke, Pierangelo Veggiotti, Tobias Loddenkemper, Gaetan Lesca, Ulrike B. S. Hedrich, Silvana Franceschetti, Elena Gardella, Irina Mishina, María Vaccarezza, Timo Roser

Publikováno v: Johannesen, K M, Liu, Y, Koko, M, Gjerulfsen, C E, Sonnenberg, L, Schubert, J, Fenger, C D, Eltokhi, A, Rannap, M, Koch, N A, Lauxmann, S, Krüger, J, Kegele, J, Canafoglia, L, Franceschetti, S, Mayer, T, Rebstock, J, Zacher, P, Ruf, S, Alber, M, Sterbova, K, Lassuthová, P, Vlckova, M, Lemke, J R, Platzer, K, Krey, I, Heine, C, Wieczorek, D, Kroell-Seger, J, Lund, C, Klein, K M, Au, P Y B, Rho, J M, Ho, A W, Masnada, S, Veggiotti, P, Giordano, L, Accorsi, P, Hoei-Hansen, C E, Striano, P, Zara, F, Verhelst, H, Verhoeven, J S, Braakman, H M H, van der Zwaag, B, Harder, A V E, Brilstra, E, Pendziwiat, M, Lebon, S, Vaccarezza, M, Le, N M, Christensen, J, Grønborg, S, Scherer, S W, Howe, J, Fazeli, W, Howell, K B, Leventer, R, Stutterd, C, Walsh, S, Gerard, M, Gerard, B, Matricardi, S, Bonardi, C M, Sartori, S, Berger, A, Hoffman-Zacharska, D, Mastrangelo, M, Darra, F, Vøllo, A, Motazacker, M M, Lakeman, P, Nizon, M, Betzler, C, Altuzarra, C, Caume, R, Roubertie, A, Gélisse, P, Marini, C, Guerrini, R, Bilan, F, Tibussek, D, Koch-Hogrebe, M, Perry, M S, Ichikawa, S, Dadali, E, Sharkov, A, Mishina, I, Abramov, M, Kanivets, I, Korostelev, S, Kutsev, S, Wain, K E, Eisenhauer, N, Wagner, M, Savatt, J M, Müller-Schlüter, K, Bassan, H, Borovikov, A, Nassogne, M C, Destrée, A, Schoonjans, A S, Meuwissen, M, Buzatu, M, Jansen, A, Scalais, E, Srivastava, S, Tan, W H, Olson, H E, Loddenkemper, T, Poduri, A, Helbig, K L, Helbig, I, Fitzgerald, M P, Goldberg, E M, Roser, T, Borggraefe, I, Brünger, T, May, P, Lal, D, Lederer, D, Rubboli, G, Heyne, H O, Lesca, G, Hedrich, U B S, Benda, J, Gardella, E, Lerche, H & Møller, R S 2022, ' Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications ', Brain, vol. 145, no. 9, pp. 2991-3009 . https://doi.org/10.1093/brain/awab321
Johannesen, K M, Liu, Y, Koko, M, Gjerulfsen, C E, Sonnenberg, L, Schubert, J, Fenger, C D, Eltokhi, A, Rannap, M, Koch, N A, Lauxmann, S, Krüger, J, Kegele, J, Canafoglia, L, Franceschetti, S, Mayer, T, Rebstock, J, Zacher, P, Ruf, S, Alber, M, Sterbova, K, Lassuthová, P, Vlckova, M, Lemke, J R, Platzer, K, Krey, I, Heine, C, Wieczorek, D, Kroell-Seger, J, Lund, C, Klein, K M, Au, P Y B, Rho, J M, Ho, A W, Masnada, S, Veggiotti, P, Giordano, L, Accorsi, P, Hoei-Hansen, C E, Striano, P, Zara, F, Verhelst, H, Verhoeven, J S, Braakman, H M H, van der Zwaag, B, Harder, A V E, Brilstra, E, Pendziwiat, M, Lebon, S, Vaccarezza, M, Le, N M, Christensen, J, Grønborg, S, Scherer, S W, Howe, J, Fazeli, W, Howell, K B, Leventer, R, Stutterd, C, Walsh, S, Gerard, M, Gerard, B, Matricardi, S, Bonardi, C M, Sartori, S, Berger, A, Hoffman-Zacharska, D, Mastrangelo, M, Darra, F, Vøllo, A, Motazacker, M M, Lakeman, P, Nizon, M, Betzler, C, Altuzarra, C, Caume, R, Roubertie, A, Gélisse, P, Marini, C, Guerrini, R, Bilan, F, Tibussek, D, Koch-Hogrebe, M, Perry, M S, Ichikawa, S, Dadali, E, Sharkov, A, Mishina, I, Abramov, M, Kanivets, I, Korostelev, S, Kutsev, S, Wain, K E, Eisenhauer, N, Wagner, M, Savatt, J M, Müller-Schlüter, K, Bassan, H, Borovikov, A, Nassogne, M C, Destrée, A, Schoonjans, A S, Meuwissen, M, Buzatu, M, Jansen, A, Scalais, E, Srivastava, S, Tan, W H, Olson, H E, Loddenkemper, T, Poduri, A, Helbig, K L, Helbig, I, Fitzgerald, M P, Goldberg, E M, Roser, T, Borggraefe, I, Brünger, T, May, P, Lal, D, Lederer, D, Rubboli, G, Heyne, H O, Lesca, G, Hedrich, U B S, Benda, J, Gardella, E, Lerche, H & Møller, R S 2022, ' Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications ', Brain : a journal of neurology, vol. 145, no. 9, pp. 2991-3009 . https://doi.org/10.1093/brain/awab321
Brain
Johannesen, K M, Liu, Y, Koko, M, Gjerulfsen, C E, Sonnenberg, L, Schubert, J, Fenger, C D, Eltokhi, A, Rannap, M, Koch, N A, Lauxmann, S, Krüger, J, Kegele, J, Canafoglia, L, Franceschetti, S, Mayer, T, Rebstock, J, Zacher, P, Ruf, S, Alber, M, Sterbova, K, Lassuthová, P, Vlckova, M, Lemke, J R, Platzer, K, Krey, I, Heine, C, Wieczorek, D, Kroell-Seger, J, Lund, C, Klein, K M, Au, P Y B, Rho, J M, Ho, A W, Masnada, S, Veggiotti, P, Giordano, L, Accorsi, P, Hoei-Hansen, C E, Striano, P, Zara, F, Verhelst, H, Verhoeven, J S, Braakman, H M H, van der Zwaag, B, Harder, A V E, Brilstra, E, Pendziwiat, M, Lebon, S, Vaccarezza, M, le, N M, Christensen, J, Grønborg, S, Scherer, S W, Howe, J, Fazeli, W, Howell, K B, Leventer, R, Stutterd, C, Walsh, S, Gerard, M, Gerard, B N, Matricardi, S, Bonardi, C M, Sartori, S, Berger, A, Hoffman-Zacharska, D, Mastrangelo, M, Darra, F, Vøllo, A, Motazacker, M M, Lakeman, P, Nizon, M, Betzler, C, Altuzarra, C, Caume, R, Roubertie, A, Gélisse, P, Marini, C, Guerrini, R, Bilan, F, Tibussek, D, Koch-Hogrebe, M, Perry, M S, Ichikawa, S, Dadali, E, Sharkov, A, Mishina, I, Abramov, M, Kanivets, I, Korostelev, S, Kutsev, S, Wain, K E, Eisenhauer, N, Wagner, M, Savatt, J M, Müller-Schlüter, K, Bassan, H, Borovikov, A, Nassogne, M C, Destrée, A, Schoonjans, A S, Meuwissen, M, Buzatu, M, Jansen, A, Scalais, E, Srivastava, S, Tan, W H, Olson, H E, Loddenkemper, T, Poduri, A, Helbig, K L, Helbig, I, Fitzgerald, M P, Goldberg, E M, Roser, T, Borggraefe, I, Brünger, T, May, P, Lal, D, Lederer, D, Rubboli, G, Heyne, H O, Lesca, G, Hedrich, U B S, Benda, J, Gardella, E, Lerche, H & Møller, R S 2022, ' Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications ', Brain, vol. 145, no. 9, pp. 2991-3009 . https://doi.org/10.1093/brain/awab321
Brain, 145(9), 2991-3009. Oxford University Press

We report detailed functional analyses and genotype-phenotype correlations in 392 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel Nav1.6, with the aim of describing clinical phenotypes related to functio

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::75d3de186f73a35fb1500a80403bc648
https://doi.org/10.1093/brain/awab321

In vitro effects of eslicarbazepine (S-licarbazepine) as a potential precision therapy on SCN8A variants causing neuropsychiatric disorders

Autor: Erva Bayraktar, Yuanyuan Liu, Lukas Sonnenberg, Ulrike B. S. Hedrich, Yildirim Sara, Ahmed Eltokhi, Hang Lyu, Holger Lerche, Thomas V. Wuttke, Stephan Lauxmann

Publikováno v: British journal of pharmacologyREFERENCES.

Variants in SCN8A, the NaWe investigated the therapeutic potential of eslicarbazepine (S-licarbazepine; S-lic), an enhancer of slow inactivation of voltage gated sodium channels, on two variants with biophysical and neuronal gain-of-function (G1475R

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bab9452ff0aee2db06f679bd92eefc22
https://pubmed.ncbi.nlm.nih.gov/36321697

4-Aminopyridine is a promising treatment option for patients with gain-of-function KCNA2 -encephalopathy

Autor: José M. Serratosa, Kathleen M. Gorman, Dragan Marjanovic, Adrian Binelli, Niklas Schwarz, Kirsten Torge, Guido Rubboli, Monika Fudali, Harshad Pannikkaveettil Ashraf, Sanjay M. Sisodiya, Ulrike B. S. Hedrich, Matthis Synofzik, Mary D. King, Lily C. Wong-Kisiel, Pu Yan, Bruria Ben Zeev, Pedro Martínez-Ulloa, Holger Lerche, Michal Tzadok, Stephan Lauxmann, Christian Bosselmann, Thomas Bast, Markus Wolff, Florian Lutz, Nicholas M. Allen

Publikováno v: Science translational medicine 13(609), eaaz4957 (2021). doi:10.1126/scitranslmed.aaz4957

Developmental and epileptic encephalopathies are devastating disorders characterized by epilepsy, intellectual disability, and other neuropsychiatric symptoms, for which available treatments are largely ineffective. Following a precision medicine app

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::afb3cf4423213ffbf936fc3d43041809
https://doi.org/10.1126/scitranslmed.aaz4957

Genotype-phenotype correlations in SCN8A-related disorders reveal prognostic and therapeutic implications

Autor: Arve Vøllo, Stephen W. Scherer, Elena Gardella, Irina Mishina, María Vaccarezza, Jennifer L. Howe, Sebastian Lebon, Josua Kegele, Gaetan Lesca, Timo Roser, Silvia Masnada, Johannes Rebstock, Marga Buzatu, Damien Lederer, Ingo Borggraefe, Tobias Brünger, Ulrike B. S. Hedrich, Sergey Korostelev, Frédéric Bilan, Ahmed Eltokhi, M. Mahdi Motazacker, Karen E. Wain, Susanne Ruf, Manuela Pendziwiat, Lukas Sonnenberg, Yuanyuan Liu, Alice W Ho, Silvana Franceschetti, Jan Benda, Ethan M. Goldberg, Helene Verhelst, Julian Schubert, Juliann M. Savatt, Mathilde Nizon, Caroline Lund, Katherine B. Howell, Tobias Loddenkemper, Katherine L. Helbig, Cornelia Betzler, Roseline Caume, Francesca Darra, Richard J. Leventer, Christina Fenger, Pierangelo Veggiotti, Ilona Krey, Nancy Eisenhauer, Andrea Berger, Pasquale Striano, Heather E. Olson, An-Sofie Schoonjans, M Scott Perry, Stephan Lauxmann, Emmanuel Scalais, Petra Laššuthová, Monisa D. Wagner, Ilya V. Kanivets, A. A. Sharkov, P Y Billie Au, Mahmoud Koko, Siddharth Srivastava, Jakob Christensen, Artem Borovikov, Mette U Schmidt-Petersen, Anna Jansen, Judith S. Verhoeven, Johanna Krüger, Claudia M Bonardi, Shoji Ichikawa, Patrick May, Sabine Grønborg, Johannes R. Lemke, Marije Meuwissen, Katalin Sterbova, Mark Fitzgerald, Lucio Giordano, Holger Lerche, Mikhail Abramov, Bénédicte Gérard, Elena L. Dadali, Cecilia Altuzarra, Aster V. E. Harder, Stefano Sartori, Katrine M Johannesen, Sergey Kutsev, Maert Rannap, Renzo Guerrini, Dagmar Wieczorek, Laura Canafoglia, Annapurna Poduri, Christina E. Hoei-Hansen, Agathe Roubertie, Nils A Koch, Karen Müller-Schlüter, Chloe A Stutterd, Ngoc Minh Le, Pia Zacher, Constanze Heine, Sonja Walsh, Carla Marini, Federico Zara, Karl Martin Klein, Eva H. Brilstra, Guido Rubboli, Walid Fazeli, Judith Kroell-Seger, Rikke S. Møller, Dorota Hoffman-Zacharska, Michael Alber, Phillis Lakeman, Massimo Mastrangelo, Margarete Koch-Hogrebe, Ingo Helbig, Daniel Tibussek, Marketa Vlckova, Anne Destrée, Wen-Hann Tan, Haim Bassan, Dennis Lal, Patrizia Accorsi, Bert van der Zwaag, Cathrine E Gjerulfsen, Marion Gérard, Sara Matricardi, Thomas U. Mayer, Philippe Gelisse, Jong M. Rho, Marie-Cécile Nassogne

We report detailed functional analyses and genotype-phenotype correlations in 433 individuals carrying disease-causing variants in SCN8A, encoding the voltage-gated Na+ channel NaV1.6. Five different clinical subgroups could be identified: 1) Benign

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::35d884802200fc5b70287f52bd03bbc0
https://doi.org/10.1101/2021.03.22.21253711