Review
Biochemistry & Molecular Biology
Martina Sandona, Giorgia Cavioli, Alessandra Renzini, Alessia Cedola, Giuseppe Gigli, Dario Coletti, Timothy A. McKinsey, Viviana Moresi, Valentina Saccone
Summary: Histone deacetylases (HDACs) regulate the deacetylation of proteins, affecting cellular processes. Abnormal HDAC expression or activity is associated with various pathologies, making them potential therapeutic targets. For example, HDAC inhibitors have shown positive effects in preclinical and clinical studies for Duchenne Muscular Dystrophy (DMD). Understanding the cellular functions of HDACs in dystrophic muscles provides new insights for the development of effective therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Chemistry, Multidisciplinary
Ilaria Cavallina, Rossella D'Alessandro, Chiara Brusa, Elisa Panero, Enrica Rolle, Francesca Rossi, Tiziana Mongini, Federica Silvia Ricci
Summary: Congenital muscular dystrophies (CMDs) are a group of genetic neuromuscular disorders characterized by delayed acquisition of motor milestones and muscle weakness. This review aims to summarize the current knowledge of motor function in pediatric patients with CMDs and the assessment tools used. The study found that motor functional aspects in CMD patients are still underinvestigated, possibly due to the rarity and phenotypic variability of these conditions. The assessment scales and age groups considered varied among studies, and overall, there is a lack of longitudinal research on motor function progression. More accurate and shared protocols for assessing motor function in CMD patients are needed.
APPLIED SCIENCES-BASEL
(2023)
Article
Ophthalmology
Xuan-thanh-an Nguyen, Mays Talib, Mary J. van Schooneveld, J. A. N. Wijnholds, Maria M. van Genderen, Nicoline E. Schalij-delfos, Caroline C. W. Klaver, Herman E. Talsma, Marta Fiocco, Ralph J. Florijn, Jacoline B. ten Brink, Frans P. M. Cremers, Magda A. Meester-smoor, L. Ingeborgh van den Born, Carel B. Hoyng, Alberta A. H. J. Thiadens, Arthur A. Bergen, Camiel J. F. Boon
Summary: This study aimed to investigate the natural disease course of retinal dystrophies associated with CRB1 and identify clinical end points for future trials. Results showed that over 2 years, BCVA and V4e isopter seeing retinal areas remained relatively stable in the entire cohort, but individual patients showed signs of clinical progression. Microperimetry revealed a significant decrease in retinal sensitivity during follow-up.
AMERICAN JOURNAL OF OPHTHALMOLOGY
(2022)
Article
Clinical Neurology
Daniel Natera-de Benito, A. Reghan Foley, Cristina Dominguez-Gonzalez, Carlos Ortez, Minal Jain, Aron Mebrahtu, Sandra Donkervoort, Ying Hu, Margaret Fink, Pomi Yun, Tracy Ogata, Julita Medina, Meritxell Vigo, Katherine G. Meilleur, Meganne E. Leach, Jahannaz Dastgir, Jordi Diaz-Manera, Laura Carrera-Garcia, Jessica Exposito-Escudero, Macarena Alarcon, Daniel Cuadras, Elena Montiel-Morillo, Jose C. Milisenda, Raul Dominguez-Rubio, Montse Olive, Jaume Colomer, Cristina Jou, Cecilia Jimenez-Mallebrera, Carsten G. Bonnemann, Andres Nascimento
Summary: This study proposed a prospective phenotypic classification for COL6-RDs based on the initial maximal motor ability achieved, which can accurately predict a patient's phenotype and improve clinical care. The early determination of a patient's COL6-RD phenotype enables better prognosis of future motor and pulmonary function, and aids in the design of future clinical trials by allowing early stratification of trial cohorts.
Review
Biochemistry & Molecular Biology
Alan Rawls, Bridget K. Diviak, Cameron I. Smith, Grant W. Severson, Sofia A. Acosta, Jeanne Wilson-Rawls
Summary: Muscular dystrophies are genetic muscle-wasting disorders characterized by chronic inflammation and fibrotic scarring in muscle tissue. Duchenne muscular dystrophy, the most common form, is typically treated with anti-inflammatory glucocorticoids; however, their long-term use is limited by adverse side effects. Developing new pharmacotherapeutic approaches to reduce muscle damage and promote repair is crucial.
Review
Cell Biology
Nicola Mosca, Sara Petrillo, Sara Bortolani, Mauro Monforte, Enzo Ricci, Fiorella Piemonte, Giorgio Tasca
Summary: Oxidative stress is a prominent factor in the pathophysiology of various muscle disorders, but specific mechanisms and targeted antioxidant therapies still require further research and clinical trials.
Article
Oncology
Yu Zhang, Takahiko Nishiyama, Eric N. Olson, Rhonda Bassel-Duby
Summary: Muscular dystrophies are a group of neuromuscular disorders with genetic causes that lead to muscle loss and degeneration. The CRISPR/Cas system offers a new path for treatment, potentially correcting genetic mutations permanently and benefiting skeletal muscle due to its post-mitotic and multinucleated features. However, challenges remain for translating CRISPR/Cas genome editing into a viable therapy for muscular dystrophies.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Biochemistry & Molecular Biology
Arlek Gonzalez-Jamett, Walter Vasquez, Gabriela Cifuentes-Riveros, Rafaela Martinez-Pando, Juan C. Saez, Ana M. Cardenas
Summary: Muscular dystrophies are a heterogeneous group of neuromuscular disorders characterized by muscle pain, weakness, and atrophy. These diseases are caused by gene mutations that affect the structure and function of skeletal muscles, leading to inflammation, oxidative stress, and muscle degeneration. Dysregulation of connexin hemichannels plays a crucial role in these processes.
Review
Immunology
Andrea Farini, Chiara Villa, Luana Tripodi, Mariella Legato, Yvan Torrente
Summary: Muscular dystrophies and inflammatory myopathies are muscular disorders characterized by progressive muscle weakness and mass loss, with shared features of inflammation and immune response. Immune mechanisms involved include complement cascade activation and auto-antibodies directed against muscular proteins.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Medicine, General & Internal
Camille Bouchard, Jacques P. Tremblay
Summary: This review article presents 39 genes associated with limb-girdle muscular dystrophies (LGMDs), which can be inherited dominantly or recessively. The classification of LGMDs has evolved over time and now requires a mutation causing proximal muscle weakness found in multiple unrelated families. The article also discusses available and developing therapies for LGMDs, aiming to address the root cause of the disease instead of treating individual symptoms.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Clinical Neurology
Jerry R. Mendell, Samiah A. Al-Zaidy, Kelly J. Lehman, Markus McColly, Linda P. Lowes, Lindsay N. Alfano, Natalie F. Reash, Megan A. Iammarino, Kathleen R. Church, Aaron Kleyn, Matthew N. Meriggioli, Richard Shell
Summary: This ongoing study evaluates the long-term safety and effectiveness of onasemnogene abeparvovec gene replacement therapy in infants with SMA type 1. The therapeutic dose showed sustained clinical benefits for patients with no need for permanent ventilation up to 6 years of age.
Review
Cardiac & Cardiovascular Systems
Chrysanthos Grigoratos, Alberto Aimo, Andrea Barison, Vincenzo Castiglione, Giancarlo Todiere, Giulia Ricci, Gabriele Siciliano, Michele Emdin
Summary: Muscular dystrophies are a group of inherited disorders with Duchenne muscular dystrophy as the most common form in childhood. Although cardiac magnetic resonance studies have largely been conducted at single centers and with small patient populations, they have provided detailed insights into cardiac involvement patterns in muscular dystrophy, leading to practical recommendations for patient management and diagnosis.
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY
(2021)
Article
Clinical Neurology
Alberto A. Zambon, Francesco Muntoni
Summary: Congenital muscular dystrophies are a group of inherited conditions characterized by muscle weakness before ambulation, delayed motor milestones, and dystrophic muscle pathology. Multiple genes, at least 35, are responsible for CMD phenotypes, leading to a wide spectrum of clinical manifestations. Recent advances in gene discovery have expanded the understanding of CMDs, with comprehensive gene panels able to provide a final diagnosis in around 60% of cases.
NEUROMUSCULAR DISORDERS
(2021)
Article
Cell Biology
Lingling Kong, David O. Valdivia, Christian M. Simon, Cera W. Hassinan, Nicolas Delestree, Daniel M. Ramos, Jae Hong Park, Celeste M. Pilato, Xixi Xu, Melissa Crowder, Chloe C. Grzyb, Zachary A. King, Marco Petrillo, Kathryn J. Swoboda, Crystal Davis, Cathleen M. Lutz, Alexander H. Stephan, Xin Zhao, Marla Weetall, Nikolai A. Naryshkin, Thomas O. Crawford, George Z. Mentis, Charlotte J. Sumner
Summary: Gene replacement and pre-mRNA splicing modifier therapies show promise as breakthrough treatments for SMA, but the mechanisms underlying their variable efficacy are not fully understood. Studies in severe infantile onset human SMA tissues and mouse models reveal the importance of early treatment in improving motor neuron development and function. Genetic restoration of survival motor neuron protein in mouse motor neurons can enhance SMA motor axon development and maintenance. Early intervention is crucial to prevent neonatal axon degeneration and optimize therapeutic outcomes for SMA patients.
SCIENCE TRANSLATIONAL MEDICINE
(2021)
Article
Biotechnology & Applied Microbiology
Enrico Almici, Vanessa Chiappini, Aristides Lopez-Marquez, Carmen Badosa, Blanca Blazquez, David Caballero, Joan Montero, Daniel Natera-de Benito, Andres Nascimento, Monica Roldan, Anna Lagunas, Cecilia Jimenez-Mallebrera, Josep Samitier
Summary: This study engineered a personalized pre-clinical model of COL6-RDs using cell-derived matrices (CDMs) technology and found alterations in ECM structure and composition in COL6-RD patients. These models may serve as promising tools to explore the pathology of COL6-RDs, identify novel biomarkers, and investigate new therapeutic targets and treatments.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Anatomy & Morphology
S. Lucibello, T. Verdolotti, F. M. Giordano, L. Lapenta, A. Infante, F. Piludu, T. Tartaglione, D. Chieffo, C. Colosimo, E. Mercuri, R. Battini
Article
Clinical Neurology
Marika Pane, Giorgia Coratti, Valeria A. Sansone, Sonia Messina, Claudio Bruno, Michela Catteruccia, Maria Sframeli, Emilio Albamonte, Marina Pedemonte, Adele D'Amico, Chiara Bravetti, Beatrice Berti, Giorgia Brigati, Paola Tacchetti, Francesca Salmin, Roberto de Sanctis, Simona Lucibello, Marco Piastra, Orazio Genovese, Enrico Bertini, Giuseppe Vita, Francesco Danilo Tiziano, Eugenio Mercuri
ANNALS OF NEUROLOGY
(2019)
Article
Clinical Neurology
Giovanni Baranello, Sabrina Signorini, Francesca Tinelli, Andrea Guzzetta, Emanuela Pagliano, Andrea Rossi, Maria Foscan, Irene Tramacere, Domenico M. M. Romeo, Daniela Ricci, Riccardo Zanin, Elisa Fazzi, Giovanni Cioni, Eugenio Mercuri
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2020)
Article
Clinical Neurology
Jacqueline Montes, Sally Dunaway Young, Elena S. Mazzone, Amy Pasternak, Allan M. Glanzman, Richard S. Finkel, Basil T. Darras, Francesco Muntoni, Eugenio Mercuri, Darryl C. De Vivo, Kathie M. Bishop, Eugene Schneider, C. Frank Bennett, Richard Foster, Wildon Farwell
Article
Multidisciplinary Sciences
Claudia Brogna, Giorgia Coratti, Marika Pane, Valeria Ricotti, Sonia Messina, Adele D'Amico, Claudio Bruno, Gianluca Vita, Angela Berardinelli, Elena Mazzone, Francesca Magri, Federica Ricci, Tiziana Mongini, Roberta Battini, Luca Bello, Elena Pegoraro, Giovanni Baranello, Stefano C. Previtali, Luisa Politano, Giacomo P. Comi, Valeria A. Sansone, Alice Donati, Enrico Bertini, Francesco Muntoni, Nathalie Goemans, Eugenio Mercuri, Valentina Lanzillotta, Emanuela Viggiano, Silvia Frosini, Andrea Barp, Enrica Rolle, Francesca Rossi, Maria Teresa Arnoldi, Lavinia Fanelli, Nicola Forcina, Francesca Salmin, Emilio Albamonte, Ksenija Gorni, Joana Pisco Dominges, Marleen van der Hauwe, Chiara Consulo, Vincenzo Di Bella, Marta Rossi, Alice Gardani, Giulia Colia, Adelina Carlesi
Article
Clinical Neurology
Basil T. Darras, Michelle A. Farrar, Eugenio Mercuri, Richard S. Finker, Richard Foster, Steven G. Hughes, Ishir Bhan, Wildon Farwell, Sarah Gheuens
Editorial Material
Clinical Neurology
Eugenio Mercuri, Sonia Messina, Jacqueline Montes, Francesco Muntoni, Valeria A. Sansone
NEUROMUSCULAR DISORDERS
(2020)
Article
Clinical Neurology
Robert C. Sergott, Giulia M. Amorelli, Giovanni Baranello, Emmanuel Barreau, Shannon Beres, Steven Kane, Eugenio Mercuri, Lorenzo Orazi, Melissa SantaMaria, Gemma Tremolada, Diletta Santarsiero, Agnieszka Waskowska, Shigeko Yashiro, Nora Denk, Sabine Furst-Recktenwald, Marianne Gerber, Ksenija Gorni, Birgit Jaber, Bjoern Jacobsen, Lutz Mueller, Stephane Nave, Renata S. Scalco, Stefania B. Marzoli
Summary: Evaluation of ophthalmologic safety in patients with spinal muscular atrophy (SMA) treated with risdiplam showed no retinal structural or functional changes, suggesting that safety ophthalmologic monitoring is not needed in these patients.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Letter
Clinical Neurology
Eugenio Mercuri, Eloisa Tiberi, Simonetta Costa, Marika Pane, Francesca Priolo, Domenico Romeo, Roberto de Sanctis, Danilo Tiziano, Giorgio Conti, Giovanni Vento
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2021)
Review
Clinical Neurology
Eugenio Mercuri
Summary: This paper provides a short history of spinal muscular atrophy, discussing the impact of recent therapeutic advances, new challenges in interpreting efficacy of therapies, and the importance of further research on new phenotypes and assessment methods. The need for neonatal screening is emphasized based on results in presymptomatic patients.
NEUROMUSCULAR DISORDERS
(2021)
Article
Clinical Neurology
Richard S. Finkel, Monique M. Ryan, Samuel Ignacio Pascual Pascual, John W. Day, Eugenio Mercuri, Darryl C. De Vivo, Richard Foster, Jacqueline Montes, Juliana Gurgel-Giannetti, Drew MacCannell, Zdenek Berger
Summary: This study investigates the relationship between nusinersen cerebrospinal fluid (CSF) exposure, biomarker levels, and clinical efficacy. The results indicate that higher CSF exposure of nusinersen is associated with greater efficacy. Predictions suggest that a higher dose of nusinersen can lead to increased CSF levels and improved clinical efficacy.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2022)
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)
Review
Pediatrics
Laura Antonaci, Maria Carmela Pera, Eugenio Mercuri
Summary: The natural history of spinal muscular atrophy has been significantly influenced by improved care standards and the availability of disease-modifying therapies. This paper aims to present the current therapeutic scenario and challenges associated with new phenotypes emerging years after the introduction of therapies. It also includes a review of real-world data, offering insights into the safety and effectiveness of the drugs beyond clinical trials. The paper emphasizes future perspectives, including ongoing clinical trials and advancements in the use of available drugs.
EUROPEAN JOURNAL OF PEDIATRICS
(2023)
Article
Pediatrics
Eugenio Mercuri, Giuseppe Zampino, Alisha Morsella, Marika Pane, Roberta Onesimo, Carmen Angioletti, Piero Valentini, Claudia Rendeli, Antonio Ruggiero, Lorenzo Nanni, Antonio Chiaretti, Giovanni Vento, David Korn, Emilio Meneschincheri, Paolo Sergi, Giovanni Scambia, Walter Ricciardi, Andrea Cambieri, Antonio Giulio De Belvis
Summary: The "Contactless" model provides remote services for chronic pediatric patients, covering diagnostic procedures and disease progression monitoring. Its implementation allows for personalized care, with potential for replication in other medical fields and cost savings for patients, caregivers, and healthcare professionals.
ITALIAN JOURNAL OF PEDIATRICS
(2021)
Article
Clinical Neurology
Eloisa Tiberi, Simonetta Costa, Marika Pane, Francesca Priolo, Roberto de Sanctis, Domenico Romeo, Francesco D. Tiziano, Giorgio Conti, Giovanni Vento, Eugenio Mercuri
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2020)