Article
Genetics & Heredity
G. Diane Shelton, Katie M. Minor, Ling T. Guo, Alison Thomas-Hollands, Koranda A. Walsh, Steven G. Friedenberg, Jonah N. Cullen, James R. Mickelson
Summary: This report describes a novel genetic basis for congenital dyserythropoietic anemia and polymyopathy in Labrador Retriever littermates. A nonsense variant in the EHBP1L1 gene was identified in a homozygous form in the affected dogs, leading to a premature stop codon and deletion of approximately 90% of the protein. The EHBP1L1 gene is critical to actin cytoskeletal organization and apical-directed transport in polarized epithelial cells, and its connection to BIN1 and DMN2 functions is particularly interesting.
Article
Engineering, Biomedical
Haiwang Shi, Fan Li, Fulong Zhang, Xiaobei Wei, Chengyi Liu, Rui Duan
Summary: This study investigates the effects of different frequency combinations of electrical stimulation (ES) on preventing muscle atrophy and dysfunction. The results show that high frequency ES can reduce the harmful effects of muscle unloading on muscle mass and contractile function. Furthermore, combining high frequency ES with low frequency ES is more effective in improving skeletal muscle strength and endurance.
JOURNAL OF NEUROENGINEERING AND REHABILITATION
(2023)
Article
Clinical Neurology
Carola Hedberg-Oldfors, Ulrika Lindgren, Kittichate Visuttijai, Daniel Loof, Sara Roos, Christer Thomsen, Anders Oldfors
Summary: Patients with dermatomyositis (DM) have reduced aerobic metabolism and impaired muscle function due to mitochondrial respiratory chain dysfunction. This study found that the deficiency of complexes I and IV is a major cause of the disease, while complex II is unaffected. Depletion of mitochondrial RNA and a decrease in mtDNA copy number in affected muscle regions contribute to the muscle pathology and disturbed aerobic metabolism.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2022)
Article
Multidisciplinary Sciences
Aseel Al-Shwaheen, Alaa A. A. Aljabali, Ghada Alomari, Mazhar Al Zoubi, Walhan Alshaer, Bahaa Al-Trad, Murtaza M. Tambuwala
Summary: This study found that gold nanoparticles can improve muscle atrophy in diabetic rats by reducing hyperglycemia, suppressing inflammation and oxidative stress, and inhibiting the proteolytic process of the ubiquitin-proteasome.
Article
Clinical Neurology
Gorka Fernandez-Eulate, Giorgia Querin, Ursula Moore, Anthony Behin, Marion Masingue, Guillaume Bassez, Sarah Leonard-Louis, Pascal Laforet, Thierry Maisonobe, Philippe-Edouard Merle, Marco Spinazzi, Guilhem Sole, Thierry Kuntzer, Anne-Laure Bedat-Millet, Emmanuelle Salort-Campana, Shahram Attarian, Yann Pereon, Leonard Feasson, Julie Graveleau, Aleksandra Nadaj-Pakleza, France Leturcq, Svetlana Gorokhova, Martin Krahn, Bruno Eymard, Volker Straub, Teresinha Evangelista, Tanya Stojkovic
Summary: Late-onset dysferlinopathy patients often present with more atypical clinical features, milder pathological findings, and have a later age of onset of symptoms compared to early-onset dysferlinopathy patients.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Cell Biology
Michaeljohn Kalakoutis, Ross D. D. Pollock, Norman R. R. Lazarus, R. Andrew Atkinson, Marc George, Onur Berber, Roger C. C. Woledge, Julien Ochala, Stephen D. R. Harridge
Summary: The specific force (SF) of human aging in single muscle fibers is inconsistent in different studies, which may result from variations in the health status/physical activity levels and methodological differences. This study compared SF in fibers from older hip fracture patients, healthy master cyclists, and healthy nontrained young adults using two different activating solutions. The results showed that the activating solution significantly affected the force and revealed a difference in sensitivity in muscle fibers of hip fracture patients.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Bo Song, Yating Cheng, Md. Abul Kalam Azad, Sujuan Ding, Kang Yao, Xiangfeng Kong
Summary: This study investigated the molecular basis for differences in meat yield and quality between Duroc, Taoyuan black (TB), and Xiangcun black (XB) pigs. The results show that TB pigs have higher fat percentage, intramuscular fat content, and antioxidant capacity, but lower carcass weight, lean percentage, pH decline, and glycolytic potential compared to Duroc pigs. Moreover, TB pigs have lower expression of protein synthesis and lipolysis genes in their muscles. Targeted metabolome analysis revealed significant differences in 24 metabolites among the three pig breeds. Correlation analysis suggests that l-malic acid and β-alanine contents in muscles are closely related to meat quality. These findings suggest that the excellent meat quality of TB pigs is attributed to muscle metabolism and fiber characteristics, while lower protein synthesis and lipolysis contribute to less meat yield.
Review
Geriatrics & Gerontology
Hamid Mollazadeh, Erfan Tavana, Giovanni Fanni, Simona Bo, Maciej Banach, Matteo Pirro, Stephan von Haehling, Tannaz Jamialahmadi, Amirhossein Sahebkar
Summary: Statins, commonly used for treating hyperlipidaemia, have pleiotropic effects on atherosclerosis, but can also lead to adverse reactions like myopathy. Studies indicate that statins impact mitochondrial function in various ways, potentially contributing to the onset of additional pathological conditions.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Article
Biochemistry & Molecular Biology
Cathrine Nordgaard, Anna Constance Vind, Amy Stonadge, Rasmus Kjobsted, Goda Snieckute, Pedro Antas, Melanie Blasius, Marie Sofie Reinert, Ana Martinez Del Val, Dorte Breinholdt Bekker-Jensen, Peter Haahr, Yekaterina A. Miroshnikova, Abdelghani Mazouzi, Sarah Falk, Emeline Perrier-Groult, Christopher Tiedje, Xiang Li, Jens Rithamer Jakobsen, Nicolas Oldenburg Jorgensen, Jorgen F. P. Wojtaszewski, Frederic Mallein-Gerin, Jesper Lovind Andersen, Cristian Pablo Pennisi, Christoffer Clemmensen, Moustapha Kassem, Abbas Jafari, Thijn Brummelkamp, Vivian S. W. Li, Sara A. Wickstrom, Jesper Velgaard Olsen, Gonzalo Blanco, Simon Bekker-Jensen
Summary: This study reveals the mechanisms by which muscle fibers sense mechanical load to activate p38 and JNK signaling. ZAK is able to recognize stress fibers in cells and Z-discs in muscle fibers under mechanical stress. ZAK deficiency leads to skeletal muscle defects and changes in myosin profile.
Article
Clinical Neurology
Nuria Muelas, Marina Frasquet, Fernando Mas-Estelles, Pilar Marti, Laura Martinez-Vicente, Teresa Sevilla, Inmaculada Azorin, Javier Poyatos-Garcia, Herminia Argente-Escrig, Roger Vilchez, Juan F. Vazquez-Costa, Luis Bataller, Juan J. Vilchez
Summary: Laing myopathy exhibits broad clinical and pathological variability, with muscle imaging profiles providing valuable insights and imaging analysis validated as an outcome measure. Various imaging features are correlated with age at onset, disease duration, and clinical manifestations, demonstrating the usefulness of imaging analysis in categorizing patients and monitoring disease progression over time.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Cell Biology
Alexander Sonne, Lorenzo Peverelli, Aurelio Hernandez-Lain, Cristina Dominguez-Gonzalez, Jesper L. Andersen, Margherita Milone, Alan H. Beggs, Julien Ochala
Summary: In this study, we investigated the effects of MYH2 truncating mutations on the presence and post-translational modifications of myosin heavy chains, as well as the functionality of myosin molecules. We found that these mutations resulted in the presence of type IIa myosin heavy chains with an additional acetylated lysine in patients, accompanied by increased ATP demand, faster actomyosin kinetics, and reduced muscle fiber force.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Paola Aguiari, Yan-Yun Liu, Astgik Petrosyan, Sheue-yann Cheng, Gregory A. Brent, Laura Perin, Anna Milanesi
Summary: Thyroid hormone signaling, particularly through the interaction between COUP-TFII and THRA, plays a crucial role in muscle development and function, as well as in the maintenance of muscle mass. COUP-TFII is identified as a key factor in the abnormal muscle phenotype observed in THRA-PV mice, contributing to accelerated skeletal muscle loss with aging and impaired muscle regeneration after injury.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Alexandre Prola, Jordan Blondelle, Aymeline Vandestienne, Jerome Piquereau, Raphael G. P. Denis, Stephane Guyot, Hadrien Chauvin, Arnaud Mourier, Marie Maurer, Celine Henry, Nahed Khadhraoui, Cindy Gallerne, Thibaut Molinie, Guillaume Courtin, Laurent Guillaud, Melanie Gressette, Audrey Solgadi, Florent Dumont, Julien Castel, Julien Ternacle, Jean Demarquoy, Alexandra Malgoyre, Nathalie Koulmann, Genevieve Derumeaux, Marie-France Giraud, Frederic Joubert, Vladimir Veksler, Serge Luquet, Frederic Relaix, Laurent Tiret, Fanny Pilot-Storck
Summary: Mice deficient for a muscle-specific enzyme of very-long-chain fatty acid synthesis displayed increased basal energy expenditure and protection against high-fat diet-induced obesity. Muscle-specific modulation of the very-long-chain fatty acid pathway was associated with a reduced content of inner mitochondrial membrane phospholipid cardiolipin and a blunted coupling efficiency between the respiratory chain and ATP synthase, which was restored by cardiolipin enrichment. Selective increase of lipid oxidative capacities in skeletal muscle, through the cardiolipin-dependent lowering of mitochondrial ATP production, provides an effective option against obesity at the whole-body level.
Article
Genetics & Heredity
G. Diane Shelton, Katie M. Minor, Steven G. Friedenberg, Jonah N. Cullen, Ling T. Guo, James R. Mickelson
Summary: The spectrum of canine muscular dystrophies has expanded rapidly with the identification of more affected breeds and associated mutations. Gene defects in the sarcolemma and the extracellular matrix have been found to be responsible for various forms of muscular dystrophies. Whole genome sequencing and whole exome sequencing have helped to discover new causative mutations. In this report, new forms of X-linked muscular dystrophy in Brittany spaniels and a French bulldog are described.
Review
Cardiac & Cardiovascular Systems
Diana Maria Ronderos-Botero, Arundhati Dileep, Laura Yapor, Ravish Singhal
Summary: The reciprocal interaction between the heart and lung, known as cardiopulmonary coupling (CPC), plays a crucial role in maintaining the functional and anatomical reserve of the body. However, disruptions in CPC can occur in patients with cardiac or pulmonary pathologies as well as those with myopathies. This article presents a case of nemaline myopathy (NM) and reviews the literature on the effects of myopathy-related disruption of CPC on cardiac and pulmonary function.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Clinical Neurology
Drew MacCannell, Zdenek Berger, Janbernd Kirschner, Eugenio Mercuri, Michelle A. Farrar, Susan T. Iannaccone, Nancy L. Kuntz, Richard S. Finkel, Marta Valente, Francesco Muntoni
Summary: This study investigated the dosing regimens for the fastest restoration of steady-state concentrations of nusinersen in the cerebrospinal fluid (CSF) after a treatment interruption during maintenance dosing. The results showed that two doses of nusinersen at 14-day intervals are optimal for treatment interruptions of >= 8 to < 16 months since the last dose, while three doses at 14-day intervals are optimal for treatment interruptions of >= 16 to < 40 months. Interruptions of >= 40 months require the full loading regimen to rapidly restore nusinersen levels in CSF.
Article
Clinical Neurology
Eugenio Mercuri, Nicolas Deconinck, Elena S. Mazzone, Andres Nascimento, Maryam Oskoui, Kayoko Saito, Carole Vuillerot, Giovanni Baranello, Odile Boespflug-Tanguy, Nathalie Goemans, Janbernd Kirschner, Anna Kostera-Pruszczyk, Laurent Servais, Marianne Gerber, Ksenija Gorni, Omar Khwaja, Heidemarie Kletzl, Renata S. Scalco, Hannah Staunton, Wai Yin Yeung, Carmen Martin, Paulo Fontoura, John W. Day
Summary: Risdiplam has shown significant improvement in motor function compared to placebo in patients with type 2 or non-ambulant type 3 spinal muscular atrophy. Motor function generally improved in younger patients and stabilized in older patients.
Correction
Clinical Neurology
Drew MacCannell, Zdenek Berger, Lilly East, Eugenio Mercuri, Janbernd Kirschner, Francesco Muntoni, Michelle A. Farrar, Joanna Peng, Jie Zhou, Ivan Nestorov, Wildon Farwell, Richard S. Finkel
NEUROMUSCULAR DISORDERS
(2022)
Article
Clinical Neurology
Johanna Holzwarth, Nadja Minopoli, Charlotte Pfrimmer, Martin Smitka, Sabine Borrel, Janbernd Kirschner, Nicole Muschol, Hans Hartmann, Julia B. Hennermann, Bernd A. Neubauer, Elke Hobbiebrunken, Ralf Husain, Andreas Hahn
Summary: Little is known about the clinical symptomatology and genetics of juvenile onset Pompe disease (JOPD). However, this study found that the phenotype of JOPD is broad and there is poor correlation between genotype and phenotype in these patients.
Article
Clinical Neurology
Astrid Pechmann, Thorsten Langer, Janbernd Kirschner
Summary: The aim of this study was to evaluate parents' perspectives on the process of decision-making regarding ventilator support in children with SMA type 1. The results showed that parents felt that they were not adequately informed about the disease and treatment options during the first informed consent discussions. They also found that their attitude towards ventilator support and contact with other affected families or patient advocacy groups were more likely to influence the decision of whether or not to offer ventilator support.
Article
Clinical Neurology
Astrid Pechmann, Max Behrens, Katharina Doernbrack, Adrian Tassoni, Sabine Stein, Sibylle Vogt, Daniela Zoeller, Gunther Bernert, Tim Hagenacker, Ulrike Schara-Schmidt, Inge Schwersenz, Maggie C. Walter, Matthias Baumann, Manuela Baumgartner, Marcus Deschauer, Astrid Eisenkoelbl, Marina Flotats-Bastardas, Andreas Hahn, Veronka Horber, Ralf A. Husain, Sabine Illsinger, Jessika Johannsen, Cornelia Koehler, Heike Koelbel, Monika Mueller, Arpad von Moers, Kurt Schlachter, Gudrun Schreiber, Oliver Schwartz, Martin Smitka, Elisabeth Steiner, Eva Stoegmann, Regina Trollmann, Katharina Vill, Claudia Weiss, Gert Wiegand, Andreas Ziegler, Hanns Lochmueller, Janbernd Kirschner
Summary: This study presents real-world evidence on the effects of nusinersen treatment in patients with early-onset spinal muscular atrophy. The findings demonstrate significant improvements in motor function, particularly in children under the age of 2. However, the improvements in bulbar and respiratory function are not equivalent to those in motor function.
Article
Clinical Neurology
Eugenio Mercuri, Giovanni Baranello, Odile Boespflug-Tanguy, Liesbeth De Waele, Nathalie Goemans, Janbernd Kirschner, Riccardo Masson, Elena S. Mazzone, Astrid Pechmann, Maria Carmela Pera, Carole Vuillerot, Silvia Bader-Weder, Marianne Gerber, Ksenija Gorni, Janine Hoffart, Heidemarie Kletzl, Carmen Martin, Tammy McIver, Renata S. Scalco, Wai Yin Yeung, Laurent Servais
Summary: The study demonstrated a twofold increase in SMN protein after treatment with risdiplam, suggesting its potential effectiveness in treating spinal muscular atrophy. Additionally, the safety profile of risdiplam supported the continuation of the pivotal Part 2 study.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Maryam Oskoui, John W. Day, Nicolas Deconinck, Elena S. Mazzone, Andres Nascimento, Kayoko Saito, Carole Vuillerot, Giovanni Baranello, Nathalie Goemans, Janbernd Kirschner, Anna Kostera-Pruszczyk, Laurent Servais, Gergely Papp, Ksenija Gorni, Heidemarie Kletzl, Carmen Martin, Tammy McIver, Renata S. Scalco, Hannah Staunton, Wai Yin Yeung, Paulo Fontoura, Eugenio Mercuri, SUNFISH Working Grp
Summary: Risdiplam, an oral SMN2 pre-mRNA splicing modifier, has been approved for the treatment of SMA. The SUNFISH Part 2 study demonstrated the efficacy and safety of risdiplam in type 2 and non-ambulant type 3 SMA. After 12 months of treatment, motor function improvements were maintained or further improved upon at month 24.
JOURNAL OF NEUROLOGY
(2023)
Review
Economics
Erik Landfeldt, Sophia Abner, Astrid Pechmann, Thomas Sejersen, Hugh J. McMillan, Hanns Lochmueller, Janbernd Kirschner
Summary: The objective of this study was to review and synthesize the evidence of caregiver burden in spinal muscular atrophy (SMA). The results showed that caregiving in SMA is associated with impaired health-related quality of life, family function, and mental well-being. However, there is limited evidence on the impact of disease-modifying drugs on caregiver burden. Further research is needed to better understand the clinical implications of informal caregiving in SMA and the effectiveness of new treatments.
Article
Clinical Neurology
Astrid Pechmann, Max Behrens, Katharina Doernbrack, Adrian Tassoni, Franziska Wenzel, Sabine Stein, Sibylle Vogt, Daniela Zoeller, Gunther Bernert, Tim Hagenacker, Ulrike Schara-Schmidt, Maggie C. Walter, Meike Steinbach, Astrid Blaschek, Matthias Baumann, Manuela Baumgartner, Benedikt Becker, Marina Flotats-Bastardas, Johannes Friese, Rene Guenther, Andreas Hahn, Hanna Kuepper, Jessika Johannsen, Christoph Kamm, Jan Christoph Koch, Cornelia Koehler, Heike Koelbel, Kirsten Kolzter, Arpad von Moers, Steffen Naegel, Christoph Neuwirth, Susanne Petri, Annekathrin Roediger, Mareike Schimmel, Bertold Schrank, Gudrun Schreiber, Martin Smitka, Christian Stadler, Elisabeth Steiner, Eva Stogmann, Regina Trollmann, Matthias Tuerk, Markus Weiler, Corinna Stoltenburg, Ekkehard Willichowsky, Daniel Zeller, Andreas Ziegler, Hanns Lochmueller, Janbernd Kirschner
Summary: This study reported data from the SMArtCARE registry of ambulant patients with spinal muscular atrophy (SMA) treated with nusinersen. The results showed a positive effect of nusinersen treatment in most ambulant pediatric and adult SMA patients. Not only did they observe stabilization of disease progression or lack of deterioration, but clinically meaningful improvements in walking distance.
JOURNAL OF NEUROMUSCULAR DISEASES
(2023)
Article
Clinical Neurology
Claudia A. A. Chiriboga, Claudio Bruno, Tina Duong, Dirk Fischer, Eugenio Mercuri, Janbernd Kirschner, Anna Kostera-Pruszczyk, Birgit Jaber, Ksenija Gorni, Heidemarie Kletzl, Imogen Carruthers, Carmen Martin, Francis Warren, Renata S. S. Scalco, Kathryn R. R. Wagner, Francesco Muntoni
Summary: This study investigated the safety and pharmacodynamics of risdiplam in patients with spinal muscular atrophy (SMA) who had been previously treated. The results showed that the safety and pharmacokinetics of risdiplam in previously treated patients were consistent with treatment-naive patients.
NEUROLOGY AND THERAPY
(2023)
Article
Neurosciences
David C. Schorling, Rainer Rawer, Imke Kuhlmann, Cornelia Mueller, Astrid Pechmann, Janbernd Kirschner
Summary: The study aimed to establish reference data for the 4 stair climb test (4SC), and for mechanographic analysis of ascent (4SC-Up) and descent (4SC-Dn) in healthy children and adolescents. The results showed that mechanographic analysis of the 4SC appears to be a promising tool for evaluating muscle strength and function of the lower extremities.
JOURNAL OF MUSCULOSKELETAL & NEURONAL INTERACTIONS
(2023)
Meeting Abstract
Clinical Neurology
Laurent Servais, Darryl De Vivo, Janbernd Kirschner, Eugenio Mercuri, Francesco Muntoni, Eduardo Tizzano, Susana Quijano-Roy, Kayoko Saito, Melissa Menier, Nicole LaMarca, Fred Anderson, Omar Dabbous, Richard Finkel
Meeting Abstract
Clinical Neurology
Laurent Servais, Darryl De Vivo, Janbernd Kirschner, Eugenio Mercuri, Francesco Muntoni, Eduardo Tizzano, Susana Quijano-Roy, Kayoko Saito, Melissa Menier, Nicole LaMarca, Fred Anderson, Omar Dabbous, Richard Finkel
Meeting Abstract
Biochemistry & Molecular Biology
Axel Schmidt, Tzung-Chien Hsieh, Alexej Knaus, Sophia Peters, Elisabeth Mangold, Martina Kreiss, Janbernd Kirschner, Hartmut Engels, Peter M. Krawitz
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)