Article
Clinical Neurology
Malavika A. Nair, Zhiyv Niu, Nicholas N. Madigan, Alexander Y. Shin, Jeffrey S. Brault, Nathan P. Staff, Christopher J. Klein
Summary: Current CMT trials are exploring procedural and molecular therapeutic options with significant involvement of the pharmaceutical industry globally. Emerging drug therapies targeting molecular pathogenesis are being advanced in human clinical trials; however, the majority remain in animal investigations.
FRONTIERS IN NEUROLOGY
(2023)
Article
Clinical Neurology
Vera Fridman, Stefan Sillau, Jacob Bockhorst, Kaitlin Smith, Isabella Moroni, Emanuela Pagliano, Chiara Pisciotta, Guiseppe Piscosquito, Matilde Laura, Francesco Muntoni, Chelsea Bacon, Shawna Feely, Tiffany Grider, Laurie Gutmann, Rosemary Shy, Janel Wilcox, David N. Herrmann, Jun Li, Sindhu Ramchandren, Charlotte J. Sumner, Thomas E. Lloyd, John Day, Carly E. Siskind, Sabrina W. Yum, Reza Sadjadi, Richard S. Finkel, Steven S. Scherer, Davide Pareyson, Mary M. Reilly, Michael E. Shy
Summary: This study conducted a 5-year longitudinal natural history study on 139 patients with MPZ neuropathy and found that CMTES score was sensitive to changes in patients with axonal MPZ neuropathy but not in those with demyelinating forms. Patients with moderate baseline disease severity showed the greatest changes. These findings will inform future clinical trials of MPZ neuropathies.
ANNALS OF NEUROLOGY
(2023)
Review
Genetics & Heredity
Paulius Palaima, Jose Berciano, Kristien Peeters, Albena Jordanova
Summary: Mutations in the LRSAM1 gene have been identified as the genetic cause of CMT2P, showing both dominant and recessive forms with slightly different characteristics. There is significant phenotypic variability in patients with CMT2P, necessitating serial clinical evaluation for correct diagnosis. LRSAM1 functions as a ubiquitin ligase in cells, playing a crucial role in the pathogenesis of CMT disease.
ORPHANET JOURNAL OF RARE DISEASES
(2021)
Article
Biology
Chiara Gemelli, Alessandro Geroldi, Sara Massucco, Lucia Trevisan, Ilaria Callegari, Lucio Marinelli, Giulia Ursino, Mehrnaz Hamedani, Giulia Mennella, Silvia Stara, Giovanni Maggi, Laura Mori, Cristina Schenone, Fabio Gotta, Serena Patrone, Alessia Mammi, Paola Origone, Valeria Prada, Lucilla Nobbio, Paola Mandich, Angelo Schenone, Emilia Bellone, Marina Grandis
Summary: This study presents the results of a CMT clinic in Italy, showing that CMT1A is the most common subtype and HSPB1 and MPZ genes are related to a distinct phenotype.
Review
Biochemistry & Molecular Biology
Pierre Miniou, Michel Fontes
Summary: CMT is the most common hereditary peripheral neuropathy, divided into CMT1 and CMT2, with CMT1 being the most frequent form. There has been a significant increase in publications on CMT1 subtypes in recent years, highlighting the importance of considering long-term safety and treatment effectiveness in therapeutic development.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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
Orthopedics
Theo Francois, Jean-Baptiste Davion, Valerie Deken-Delannoy, Christophe Chantelot, Marc Saab
Summary: The aim of this retrospective study was to evaluate the outcomes of carpal tunnel release surgery in patients with HNPP. The study found that at a median follow-up of 8.5 years, more than 73% of the patients were satisfied with the results, with significant improvements in discomfort and symptom severity. No significant prognostic factors for outcome were identified. The study also provided encouraging results for cubital tunnel release surgery despite the lack of preoperative data.
JOURNAL OF HAND SURGERY-EUROPEAN VOLUME
(2023)
Review
Neurosciences
Chiara Pisciotta, Paola Saveri, Davide Pareyson
Summary: Effective drug treatment for Charcot-Marie-Tooth neuropathies (CMT) is still unavailable, with current management relying on rehabilitation therapy, surgery, and symptomatic treatment. Challenges include finding disease-modifying therapies and approaches like gene silencing, gene therapy, and compound interventions are being investigated. Various potential therapeutic strategies targeting different aspects of CMT are under development and testing.
Article
Cell Biology
Yingying Zhao, Liangguo Xie, Chao Shen, Qian Qi, Yicai Qin, Juan Xing, Dejian Zhou, Yun Qi, Zhiqiang Yan, Xinhua Lin, Rongyang Dai, Jinzhong Lin, Wei Yu
Summary: Mutations in GARS affect the deacetylation activity of SIRT2 on alpha-tubulin, leading to CMT neuropathies, while reducing SIRT2 can rescue the disease and extend lifespan.
Article
Clinical Neurology
Gulden Akdal, Koray Kocoglu, Tural Tanriverdizade, Elcin Bora, Fikret Bademkiran, Ayse Nur Yuceyar, Ozgul Ekmekci, Ihsan Sukru Sengun, Hatice Karasoy
Summary: The study aimed to investigate the postural balance of CMT patients with both vestibular and somatosensory impairments compared to those with only one type of impairment. Results showed that half of the patients had some degree of vestibular impairment, which correlated with their mCTSIB scores and vertical VOR gain.
JOURNAL OF NEUROLOGY
(2021)
Article
Pediatrics
Shani Karklinsky, Shir Kugler, Omer Bar-Yosef, Andreea Nissenkorn, Anat Grossman-Jonish, Irit Tirosh, Asaf Vivante, Ben Pode-Shakked
Summary: This study identified multiple affected individuals with neuropathy in a large family, successfully diagnosed as HNPP through genetic analysis, and revealed differences in patient phenotypic features. Thorough anamnesis can lead to the discovery of rare genetic etiologies.
ITALIAN JOURNAL OF PEDIATRICS
(2022)
Article
Endocrinology & Metabolism
Graziana Colaianni, Angela Oranger, Manuela Dicarlo, Roberto Lovero, Giuseppina Storlino, Patrizia Pignataro, Antonietta Fontana, Francesca Di Serio, Angelica Ingravallo, Giuseppe Caputo, Alfredo Di Leo, Michele Barone, Maria Grano
Summary: This study found that CMT patients have lower levels of irisin compared to healthy individuals. Among CMT patients, women have higher levels of irisin than men, despite men having higher skeletal muscle mass. These findings suggest that irisin may be associated with muscle mass and strength loss, as well as bone loss, in CMT patients.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Clinical Neurology
Jin He, Xiao-Xuan Liu, Ming-Ming Ma, Jing-Jing Lin, Jun Fu, Yi-Kun Chen, Guo-Rong Xu, Liu-Qing Xu, Zhi-Fei Fu, Dan Xu, Wen-Feng Chen, Chun-Yan Cao, Yan Shi, Yi-Heng Zeng, Jing Zhang, Xiao-Chun Chen, Ru-Xu Zhang, Ning Wang, Marina Kennerson, Dong-Sheng Fan, Wan-Jin Chen
Summary: This study identified causal missense mutations in the gene encoding seryl-tRNA synthetase 1 (SerRS) that were associated with Charcot-Marie-Tooth (CMT) disease. Whole-exome sequencing and linkage analysis revealed the correlation between these mutations and the clinical phenotype in affected families. Experimental evidence demonstrated that the mutant SerRS proteins had reduced aminoacylation activity and abnormal dimerization, leading to impaired protein synthesis and induction of eIF2 alpha phosphorylation.
ANNALS OF NEUROLOGY
(2023)
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.
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
Neurosciences
Mahima Kapoor, Mary M. Reilly, Hadi Manji, Michael P. Lunn, S. Carr Aisling
Summary: High-dose IVIg has been proven to be safe and effective in restoring strength and ability to participate in daily activities for patients with CIDP and MMNCB. Individualized assessment plays a crucial role in improving treatment outcomes.
INTERNATIONAL JOURNAL OF NEUROSCIENCE
(2022)
Article
Clinical Neurology
Simina Ticau, Gautham Sridharan, Shira Tsour, William L. Cantley, Amy Chan, Jason A. Gilbert, David Erbe, Emre Aldinc, Mary M. Reilly, David Adams, Michael Polydefkis, Kevin Fitzgerald, Akshay Vaishnaw, Paul Nioi
Summary: This study identified changes in proteome associated with onset and progression of hATTR amyloidosis, with findings suggesting that NfL may serve as a biomarker of nerve damage and polyneuropathy in ATTRv amyloidosis, enabling earlier diagnosis and disease progression monitoring. Results showed patisiran treatment trending the proteome of patients towards healthy controls and significantly correlating with reduced NfL levels and neuropathy impairment score improvement.
Article
Clinical Neurology
Sindhu Ramchandren, Tong Tong Wu, Richard S. Finkel, Carly E. Siskind, Shawna M. E. Feely, Joshua Burns, Mary M. Reilly, Timothy Estilow Ot, Michael E. Shy
Summary: The study identified 6 domains relevant to quality of life in children with CMT through systematic literature reviews and analysis of generic QOL measures. A total of 60 items corresponding to those domains were developed and underwent rigorous psychometric testing to develop a reliable and valid pediatric CMT-specific quality of life outcome measure.
ANNALS OF NEUROLOGY
(2021)
Article
Clinical Neurology
Paige Howard, Shawna M. E. Feely, Tiffany Grider, Alexa Bacha, Marina Scarlato, Raffaella Fazio, Angelo Quattrini, Michael E. Shy, Stefano C. Previtali
Summary: Mutations in the Myelin Protein Zero (MPZ) gene lead to CMT1B, with toxic gain of function from the mutant protein causing neuropathy, while some patients have haploinsufficiency in the MPZ gene, mainly presenting with sensory neuropathy.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2021)
Letter
Clinical Neurology
Christopher J. Record, Menelaos Pipis, Julian Blake, Riccardo Curro, Michael P. Lunn, Alexander M. Rossor, Matilde Laura, Andrea Cortese, Mary M. Reilly
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2022)
Article
Clinical Neurology
Mahima Kapoor, Aisling Carr, Martha Foiani, Amanda Heslegrave, Henrik Zetterberg, Andrea Malaspina, Laura Compton, Elspeth Hutton, Alexander Rossor, Mary M. Reilly, Michael P. Lunn
Summary: This study found an association between plasma neurofilament light chain (pNfL) concentration and disease activity in patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), suggesting that pNfL concentration may be a useful biomarker for assessing disease remission and relapse.
EUROPEAN JOURNAL OF NEUROLOGY
(2022)
Article
Clinical Neurology
Christopher J. Record, Rana Alnasser Alsukhni, Riccardo Curro, Diego Kaski, John S. Rubin, Huw R. Morris, Andrea Cortese, Valeria Iodice, Mary M. Reilly
Summary: Biallelic repeat expansions in RFC1 have been found to cause CANVAS, a syndrome characterized by cerebellar ataxia, neuropathy, and vestibular areflexia. Additional features observed in some cases include Parkinsonism and MSA-like syndrome. We reported a case of CANVAS with severe autonomic involvement similar to classical MSA, suggesting a potential link between the two conditions.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2022)
Letter
Clinical Neurology
Christopher J. Record, Menelaos Pipis, Roy Poh, James M. Polke, Mary M. Reilly
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
Review
Clinical Neurology
Mary M. Reilly, David N. Herrmann, Davide Pareyson, Steven S. Scherer, Richard S. Finkel, Stephan Zuechner, Joshua Burns, Michael E. Shy
Summary: Heritable neurological disorders provide insights into disease mechanisms, facilitating the development of novel therapeutic approaches. The challenges of measuring disease progression in rare and slowly progressive neurogenetic diseases are addressed through the development of clinical outcome assessments and disease biomarkers in inherited peripheral neuropathies. It is proposed that carefully developed biomarkers from imaging, plasma, or skin can predict meaningful progression in functional and patient-reported outcome assessments, enabling feasible clinical trials within a shorter duration for these rare and ultra-rare disorders.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Tong Tong Wu, Richard S. S. Finkel, Carly E. E. Siskind, Shawna M. E. Feely, Joshua Burns, Mary M. M. Reilly, Francesco Muntoni, Timothy Estilow, Michael E. E. Shy, Sindhu Ramchandren
Summary: This study developed and validated the parent-proxy version of the pCMT-QOL outcome measure for children aged 8 to 18 with CMT, which is a reliable and valid measure of health-related QOL.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Clinical Neurology
Tong Tong Wu, Richard Finkel, Carly E. Siskind, Shawna M. E. Feely, Joshua Burns, Mary M. Reilly, Francesco Muntoni, Evelin Milev, Timothy Estilow, Michael E. Shy, Sindhu Ramchandren
Summary: The objective of this study was to evaluate the parent-proxy version of the pediatric Charcot Marie Tooth specific quality of life (pCMT-QOL) outcome instrument for children aged 7 or younger with CMT. The parent-proxy version of the pCMT-QOL outcome measure, known as the pCMT-QOL (0-7 years parent-proxy), was validated as a valid and sensitive proxy measure of health-related quality of life for children aged 0-7 years with CMT.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Rehabilitation
Enza Leone, Sally Davenport, Claire Robertson, Matilde Laura, Mariola Skorupinska, Mary M. Reilly, Gita Ramdharry
Summary: This study aimed to determine the incidence of PF dislocation in adults with CMT and explore the risk factors associated with it. The results showed that PF dislocation was common in CMT patients and was associated with multiple risk factors.
PHYSIOTHERAPY RESEARCH INTERNATIONAL
(2023)
Article
Clinical Neurology
Christopher P. Ptak, Tabitha A. Peterson, Jesse B. Hopkins, Christopher A. Ahern, Michael E. Shy, Robert C. Piper
Summary: Mutations in MPZ can cause various neurological disorders, and the study focuses on understanding how MPZ functions and forms oligomeric assemblies.
Review
Clinical Neurology
Caroline Kramarz, Elaine Murphy, Mary M. Reilly, Alexander M. Rossor
Summary: Nutritional peripheral neuropathies are a global issue influenced by geopolitical, cultural, and socioeconomic factors. B-vitamin deficiencies, particularly in vitamins B-1, B-2, B-6, B-9, and B-12, are the most common cause of peripheral neuropathy. This review discusses the historical and current understanding of these deficiencies, as well as diagnostic tools and genetic diseases related to B-vitamin metabolism. Endemic outbreaks of peripheral neuropathy in the past centuries further emphasize the importance of identifying and preventing nutritional deficiencies to reduce disability.
JOURNAL OF NEUROLOGY NEUROSURGERY AND PSYCHIATRY
(2023)
