Review
Genetics & Heredity
Laura Morant, Maria-Luise Erfurth, Albena Jordanova
Summary: CMT is a common neuromuscular disorder, with aaRS mutations causing different subtypes and similar clinical manifestations. Drosophila models are valuable for studying the molecular pathways of CMT and testing candidate drugs.
Review
Biochemistry & Molecular Biology
Han Zhang, Zhong-Wei Zhou, Litao Sun
Summary: Charcot-Marie-Tooth disease (CMT) is a common inherited neurodegenerative disorder with an increasing number of identified CMT-associated variants as causative factors. Recent studies have shown that in CMT, variants of Aminoacyl-tRNA synthetases (aaRS) can lead to toxic gain-of-function, and not all variants are due to the loss of aminoacylation activity. Researching the functions of these CMT-related AaRS variants is crucial for understanding the pathogenesis of CMT.
JOURNAL OF NEUROCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Samantha Mendonsa, Nicolai von Kuegelgen, Lucija Bujanic, Marina Chekulaeva
Summary: Toxic gain-of-function mutations in aminoacyl-tRNA synthetases cause degradation of peripheral motor and sensory axons known as Charcot-Marie-Tooth (CMT) disease. These mutations interfere with translation by depleting glycyl-tRNA pool and inhibiting ribosomal A-site accommodation, leading to ribosome pausing and activation of translational repression mechanisms involving the eIF2α subunit and the integrated stress response. This results in a translational repression affecting both elongation and initiation processes.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Samantha Mendonsa, Nicolai von Kuegelgen, Lucija Bujanic, Marina Chekulaeva
Summary: Toxic gain-of-function mutations in aminoacyl-tRNA synthetases cause translational repression in CMT-GARS mutant through inhibiting elongation and activating initiation via the integrated stress response.
NUCLEIC ACIDS RESEARCH
(2021)
Review
Biochemistry & Molecular Biology
Marina Stavrou, Irene Sargiannidou, Elena Georgiou, Alexia Kagiava, Kleopas A. Kleopa
Summary: CMT disease is a genetically heterogeneous disorder affecting the peripheral nerves, with diverse molecular genetic mechanisms discovered over the past three decades. There are currently various treatment approaches in preclinical testing and clinical trials, including disease-specific targeted therapies and treatments targeting common pathways shared by different CMT types. As promising treatments advance to clinical translation, optimizing outcome measures, novel biomarkers, and appropriate trial designs are crucial to facilitate successful testing and validation of novel treatments for CMT patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Clinical Neurology
Rafael Sivera, Vincenzo Lupo, Marina Frasquet, Herminia Argente-Escrig, Jorge Alonso-Perez, Jordi Diaz-Manera, Luis Querol, Maria del Mar Garcia-Romero, Samuel Ignacio Pascual, Tania Garcia-Sobrino, Carmen Paradas, Juan Francisco Vazquez-Costa, Nuria Muelas, Elvira Millet, Juan Jesus Vilchez, Carmen Espinos, Teresa Sevilla
Summary: This study identified 15 patients with CMT2Z caused by MORC2 mutations in Spain, with most exhibiting a scapuloperoneal phenotype and a few showing a neurodevelopmental phenotype. The findings suggest a diverse spectrum of disease characteristics and clinical presentations.
EUROPEAN JOURNAL OF NEUROLOGY
(2021)
Article
Cell Biology
Cara R. Schiavon, Gerald S. Shadel, Uri Manor
Summary: CMT disease is a progressive, inherited neurological disorder associated with mutations in at least 80 different genes. Clinical manifestations typically involve peripheral neurons, with some mutations potentially leading to mitochondrial mobility defects, suggesting a common underlying disease mechanism.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Laura Morant, Maria-Luise Petrovic-Erfurth, Albena Jordanova
Summary: By utilizing the improved GeneSwitch(TM) technology, we were able to regulate transgene expression in mammalian cells and fruit fly models, leading to the generation of phenotypes resembling YARS1-induced Charco-Marie-Tooth neuropathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Pharmacology & Pharmacy
Karen Libberecht, Tim Vangansewinkel, Ludo Van Den Bosch, Ivo Lambrichts, Esther Wolfs
Summary: This article reviews the role of protein quality control systems in CMT1 and introduces potential treatment strategies to restore proteostasis.
BIOCHEMICAL PHARMACOLOGY
(2023)
Review
Genetics & Heredity
Yuji Okamoto, Hiroshi Takashima
Summary: Charcot-Marie-Tooth disease (CMT) is the most common genetically transmitted neuromuscular condition without effective pharmacological treatments. The genetic heterogeneity of CMT poses a significant barrier to comprehensive therapies. This review discusses prospective therapeutic strategies for common CMT variants and evaluates the progress in gene therapy techniques, which have the potential to advance future research.
Article
Clinical Neurology
Adriana P. Rebelo, Andrea Cortese, Amit Abraham, Yael Eshed-Eisenbach, Gal Shner, Anna Vainshtein, Elena Buglo, Vladimir Camarena, Gabriel Gaidosh, Ramin Shiekhattar, Lisa Abreu, Steve Courel, Dennis K. Burns, Yunhong Bai, Chelsea Bacon, Shawna M. E. Feely, Diana Castro, Elior Peles, Mary M. Reilly, Michael E. Shy, Stephan Zuchner
Summary: The CADM family of proteins mediate direct contact and interaction between axons and glia, with mutations in CADM3 potentially causing abnormal axon-glia interaction and disease manifestation in CMT patients.
Article
Clinical Neurology
Elena Abati, Stefania Magri, Megi Meneri, Giulia Manenti, Daniele Velardo, Francesca Balistreri, Chiara Pisciotta, Paola Saveri, Nereo Bresolin, Giacomo Pietro Comi, Dario Ronchi, Davide Pareyson, Franco Taroni, Stefania Corti
Summary: This study identified two cases of biallelic HSPB1 p.S135F and p.R136L mutations in two families, confirming their association with severe CMT2F/dHMN and a strictly dominant inheritance pattern.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Article
Clinical Neurology
Marta Bellofatto, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano C. Previtali, Yuri Falzone, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Daniela Calabrese, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Luca Gentile, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Chiara Pisciotta, Davide Pareyson
Summary: This study investigated fatigue in CMT patients and found that 36% of the patients experienced abnormal fatigue. Abnormal fatigue was correlated with disease severity, anxiety, depression, sleepiness, and obesity. Therefore, the management of CMT patients should involve treating fatigue and addressing other factors such as anxiety, depression, sleepiness, and obesity.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Marta Bellofatto, Luca Gentile, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano Previtali, Marina Scarlato, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Flavio Villani, Eleonora Cavalca, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Giuseppe Didato, Chiara Pisciotta, Davide Pareyson, CMT Network
Summary: This study investigated the presence of sleep abnormalities in Charcot-Marie-Tooth disease (CMT) patients and their correlation with disease severity and characteristics. The results showed that CMT patients had poor sleep quality and daytime somnolence, which were associated with anxiety, depression, and fatigue.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Marta Bellofatto, Alessandro Bertini, Irene Tramacere, Fiore Manganelli, Gian Maria Fabrizi, Angelo Schenone, Lucio Santoro, Tiziana Cavallaro, Marina Grandis, Stefano C. Previtali, Yuri Falzone, Isabella Allegri, Luca Padua, Costanza Pazzaglia, Daniela Calabrese, Paola Saveri, Aldo Quattrone, Paola Valentino, Stefano Tozza, Luca Gentile, Massimo Russo, Anna Mazzeo, Giuseppe Vita, Sylvie Piacentini, Chiara Pisciotta, Davide Pareyson
Summary: This study investigated the presence of fatigue and its correlations in Charcot-Marie-Tooth disease (CMT). The results showed that 36% of the patients had abnormal fatigue, which was correlated with disease severity, anxiety, depression, sleepiness, and obesity. Therefore, the management of CMT patients should include treatment for fatigue and its different generators.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Editorial Material
Clinical Neurology
Maryam Oskoui, Hernan Gonorazky, Hugh J. McMillan, James J. Dowling, Reshma Amin, Cynthia Gagnon, Kathryn Selby
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Article
Clinical Neurology
Kristina M. Joyal, Jessica MacGregor, Lamia M. Hayawi, Richard J. Webster, Hugh J. McMillan
Summary: This study reviewed the volume and referral sources of nerve conduction studies (NCS) and electromyography (EMG) at a pediatric tertiary care hospital from 2014 to 2019. The findings indicate that NCS/EMG remains a valuable diagnostic tool, especially for acquired neuromuscular conditions, and can be well tolerated in children of all ages without the need for sedation.
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Letter
Clinical Neurology
Kristin D. Kernohan, Hugh J. McMillan, Ed Yeh, Melanie Lacaria, Michael Kowalski, Craig Campbell, James J. Dowling, Hernan Gonorazky, Janet Marcadier, Mark A. Tarnopolsky, Jiri Vajsar, Alex Mackenzie, Pranesh Chakraborty
CANADIAN JOURNAL OF NEUROLOGICAL SCIENCES
(2022)
Article
Biotechnology & Applied Microbiology
Hugh J. McMillan, Crystal M. Proud, Michelle A. Farrar, Ian E. Alexander, Francesco Muntoni, Laurent Servais
Summary: Gene therapy for spinal muscular atrophy (SMA) is a significant advancement in the treatment of neurologic diseases. Onasemnogene abeparvovec, a one-time gene replacement therapy, has shown improved survival and motor milestones for SMA patients. However, gene therapy is still in its early stages and faces challenges in transgene delivery.
EXPERT OPINION ON BIOLOGICAL THERAPY
(2022)
Article
Cardiac & Cardiovascular Systems
William J. Groh, Deepak Bhakta, Gordon F. Tomaselli, Ryan G. Aleong, Ricardo Alkmim Teixeira, Anthony Amato, Samuel J. Asirvatham, Yong-Mei Cha, Domenico Corrado, Denis Duboc, Zachary D. Goldberger, Minoru Horie, Joseph E. Hornyak, John Lynn Jefferies, Stefan Kaab, Jonathan M. Kalman, Naomi J. Kertesz, Neal K. Lakdawala, Pier D. Lambiase, Steven A. Lubitz, Hugh J. McMillan, Elizabeth M. McNally, Margherita Milone, Narayanan Namboodiri, Saman Nazarian, Kristen K. Patton, Vincenzo Russo, Frederic Sacher, Pasquale Santangeli, Win-Kuang Shen, Dario C. Sobral Filho, Bruce S. Stambler, Claudia Stollberger, Karim Wahbi, Xander H. T. Wehrens, Menachem Mendel Weiner, Matthew T. Wheeler, Katja Zeppenfeld
Summary: This document provides guidance for healthcare professionals in caring for patients with arrhythmic complications of neuromuscular disorders. It presents an overview of arrhythmias in different neuromuscular disorders and emphasizes the importance of managing arrhythmic cardiac manifestations.
Article
Medicine, General & Internal
Michela Guglieri, Kate Bushby, Michael P. McDermott, Kimberly A. Hart, Rabi Tawil, William B. Martens, Barbara E. Herr, Elaine McColl, Chris Speed, Jennifer Wilkinson, Janbernd Kirschner, Wendy M. King, Michelle Eagle, Mary W. Brown, Tracey Willis, Robert C. Griggs
Summary: A double-blind, parallel-group randomized clinical trial was conducted to compare the efficacy and adverse effects of different corticosteroid regimens in boys with Duchenne muscular dystrophy. The study found that daily prednisone and daily deflazacort were more effective than intermittent prednisone for improving motor function, pulmonary function, and satisfaction with treatment over a 3-year period. There was no significant difference between the two daily corticosteroid regimens.
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION
(2022)
Correction
Genetics & Heredity
Lijia Huang, Jodi Warman-Chardon, Melissa T. Carter, Kathie L. Friend, Tracy E. Dudding, Jeremy Schwartzentruber, Ruobing Zou, Peter W. Schofield, Stuart Douglas, Dennis E. Bulman, Kym M. Boycott
ORPHANET JOURNAL OF RARE DISEASES
(2022)
Article
Multidisciplinary Sciences
Jenny Setchell, Donya Mosleh, Laura McAdam, Patricia Thille, Thomas Abrams, Hugh J. McMillan, Bhavnita Mistry, Barbara E. Gibson
Summary: This paper evaluates a study that aimed to enhance clinical care for patients with muscular dystrophy and their families through regular dialogues with clinicians. The study found that the intervention led to changes in the clinical teams' thinking and practices regarding the emotional, social, and experiential aspects of living with the disease. However, there were differences between clinicians and clinics in the extent of these changes.
Article
Respiratory System
Sherri L. Katz, Jean K. Mah, Hugh J. McMillan, Craig Campbell, Vid Bijelic, Nick Barrowman, Franco Momoli, Henrietta Blinder, Shawn D. Aaron, Laura C. McAdam, The Thanh Diem Nguyen, Mark Tarnopolsky, David F. Wensley, David Zielinski, Louise Rose, Nicole Sheers, David J. Berlowitz, Lisa Wolfe, Doug McKim
Summary: This randomized controlled trial aimed to determine whether twice-daily lung volume recruitment (LVR) therapy attenuates the decline in forced vital capacity (FVC) at 2 years in boys with Duchenne muscular dystrophy (DMD). The results showed that there was no difference in decline in FVC with the use of twice-daily LVR for boys with relatively normal lung function.
Article
Biochemistry & Molecular Biology
Kevin A. Strauss, Michelle A. Farrar, Francesco Muntoni, Kayoko Saito, Jerry R. Mendell, Laurent Servais, Hugh J. McMillan, Richard S. Finkel, Kathryn J. Swoboda, Jennifer M. Kwon, Craig M. Zaidman, Claudia A. Chiriboga, Susan T. Iannaccone, Jena M. Krueger, Julie A. Parsons, Perry B. Shieh, Sarah Kavanagh, Melissa Wigderson, Sitra Tauscher-Wisniewski, Bryan E. McGill, Thomas A. Macek
Summary: Onasemnogene abeparvovec was effective and well tolerated for presymptomatic infants at risk of SMA type 2, underscoring the urgency of early identification and intervention.
Article
Biochemistry & Molecular Biology
Kevin A. Strauss, Michelle A. Farrar, Francesco Muntoni, Kayoko Saito, Jerry R. Mendell, Laurent Servais, Hugh J. McMillan, Richard S. Finkel, Kathryn J. Swoboda, Jennifer M. Kwon, Craig M. Zaidman, Claudia A. Chiriboga, Susan T. Iannaccone, Jena M. Krueger, Julie A. Parsons, Perry B. Shieh, Sarah Kavanagh, Sitra Tauscher-Wisniewski, Bryan E. McGill, Thomas A. Macek
Summary: SPR1NT (NCT03505099) is a Phase III study investigating the efficacy and safety of onasemnogene abeparvovec in presymptomatic children with biallelic SMN1 mutations. The results showed that all 14 infants enrolled in the study were able to sit independently for at least 30 seconds within 18 months and none required permanent ventilation. The treatment was well tolerated and effective for children expected to develop SMA type 1.
Article
Cardiac & Cardiovascular Systems
Di Yu, Nuanyi Liang, Julia Zebarth, Qing Shen, Miracle Ozzoude, Maged Goubran, Jennifer S. Rabin, Joel Ramirez, Christopher J. M. Scott, Fuqiang Gao, Robert Bartha, Sean Symons, Seyyed Mohammad Hassan Haddad, Courtney Berezuk, Brian Tan, Donna Kwan, Robert A. Hegele, Allison A. Dilliott, Nuwan D. Nanayakkara, Malcolm A. Binns, Derek Beaton, Stephen R. Arnott, Jane M. Lawrence-Dewar, Ayman Hassan, Dar Dowlatshahi, Jennifer Mandzia, Demetrios Sahlas, Leanne Casaubon, Gustavo Saposnik, Yurika Otoki, Krista L. Lanctot, Mario Masellis, Sandra E. Black, Richard H. Swartz, Ameer Y. Taha, Walter Swardfager
Summary: A study found that cerebral small vessel disease is associated with the ratio of certain fatty acid metabolites, and this association has not been examined in stroke patients before. The study analyzed clinical and imaging data of stroke patients and found that the ratio of these fatty acid metabolites is related to small vessel stroke, white matter hyperintensities, and temporal lobe atrophy.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2023)
Meeting Abstract
Endocrinology & Metabolism
Stefan Jackowski, Utkarsh Dang, Jinhui Ma, Maya Scharke, Victor Konji, Jacob Jaremko, Khaldoun Koujok, Mary-Ann Matzinger, Nazih Shenouda, Scott Walker, Colleen Hartigan, Lynn MacLeay, Nasrin Khan, Elizabeth Sykes, Hugh McMillan, Kerry Siminoski, Pradeep Bista, Maria Mancini, Joanne Donovan, Leanne Ward
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Meeting Abstract
Endocrinology & Metabolism
Stefan Jackowski, Utkarsh Dang, Maya Scharke, Victor Konji, Jacob Jaremko, Khaldoun Koujok, Mary-Ann Matzinger, Nazih Shenouda, Nasrin Khan, Lynn MacLeay, Elizabeth Sykes, Hugh McMillan, Kerry Siminoski, Paula Clemens, Michela Guglieri, Jean Mah, Eric Hoffman, Leanne Ward
JOURNAL OF BONE AND MINERAL RESEARCH
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Irit Hochberg, Leigh A. M. Demain, Julie Richer, Kyle Thompson, Waheeda Pagarkar, Agusti Rodriguez-Palmero Seuma, Edgard Verdura, Aurora Pujol, Albert Amberger, Andrea J. Deutschmann, Sandra Demetz, James O'Sullivan, Meredith Gillespie, Inna A. Belyantseva, Hugh J. McMillan, Melanie Barzik, Jill E. Urquhart, Alessandro Rea, Glenda M. Beaman, Simon G. Williams, Sanjeev S. Bhaskar, Isabella R. Lawrence, Emma M. Jenkinson, Jessica L. Zambonin, Zeev Blumenfeld, Sergey Yalonetsky, Stephanie Oerum, Walter Rossmanith, Wyatt W. Yue, Johannes Zschocke, Kevin J. Munro, Brendan J. Battersby, Thomas B. Friedman, Robert W. Taylor, Raymond T. O'Keefe, William G. Newman
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)