Article
Biochemistry & Molecular Biology
Francesco Fiorentini, Massimiliano Germani, Francesca Del Bene, Cinzia Pellizzoni, Sara Cazzaniga, Maurizio Rocchetti, Paolo Bettica
Summary: Givinostat (ITF2357), an oral, synthetic histone deacetylase inhibitor, significantly improved histological muscle biopsy parameters in boys with Duchenne muscular dystrophy (DMD). The pharmacokinetic (PK) model showed that givinostat PK is related to body weight. Therefore, in the Phase III DMD study, dosing of givinostat will be adjusted based on body weight and platelet counts will be monitored to ensure efficacy and safety.
EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY
(2023)
Article
Cell & Tissue Engineering
Wanling Xuan, Mahmood Khan, Muhammad Ashraf
Summary: Reprogramming hiPSCs into MPC using givinostat effectively repaired injured muscles and restored dystrophin with anti-oxidative, anti-inflammatory, and muscle gene-promoting properties.
STEM CELL RESEARCH & THERAPY
(2021)
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)
Article
Pharmacology & Pharmacy
Matteo Giovarelli, Silvia Zecchini, Giorgia Catarinella, Claudia Moscheni, Patrizia Sartori, Cecilia Barbieri, Paulina Roux-Biejat, Alessandra Napoli, Chiara Vantaggiato, Davide Cervia, Cristiana Perrotta, Emilio Clementi, Lucia Latella, Clara De Palma
Summary: Duchenne Muscular Dystrophy (DMD) is a rare genetic disorder characterized by progressive muscle wasting, weakness, and premature death. Research has shown that targeting secondary pathological mechanisms, such as mitochondrial dysfunction, is important in improving therapeutic outcomes. Studies have identified two temporally distinct phases of mitochondrial damage in DMD patients, with potential for promoting mitochondrial regeneration and enhancing energy production through specific medications.
PHARMACOLOGICAL RESEARCH
(2021)
Article
Immunology
Brigida Boccanegra, Ornella Cappellari, Paola Mantuano, Daniela Trisciuzzi, Antonietta Mele, Lisamaura Tulimiero, Michela De Bellis, Santa Cirmi, Francesca Sanarica, Alessandro Giovanni Cerchiara, Elena Conte, Ramona Meanti, Laura Rizzi, Elena Bresciani, Severine Denoyelle, Jean-Alain Fehrentz, Gabriele Cruciani, Orazio Nicolotti, Antonella Liantonio, Antonio Torsello, Annamaria De Luca
Summary: Growth hormone secretagogues (GHSs) have multiple actions including activation of GHS-receptor 1a, control of inflammation and metabolism, enhancement of GH/IGF-1-mediated myogenesis, and inhibition of angiotensin-converting enzyme. This study provides preclinical evidence for the potential benefits of GHSs in Duchenne muscular dystrophy (DMD). The results show that GHSs can improve muscle strength, reduce fibrosis-related parameters, and improve muscle metabolism in mdx mice, suggesting that GHSs have potential as therapeutic agents for DMD.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marco Ponzetti, Argia Ucci, Antonio Maurizi, Luca Giacchi, Anna Teti, Nadia Rucci
Summary: The study found that Lcn2 plays a significant role in DMD, with its overexpression being associated with bone loss. Ablating Lcn2 can reduce bone loss and improve muscle function, making it a potential therapeutic target for treating DMD-induced bone loss.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Rekha Balakrishnan, Satvik Mareedu, Gopal J. Babu
Summary: The reduction or elimination of sarcolipin (SLN) expression improves muscle metabolism, reduces oxidative stress, improves muscle pathology, and protects mdx mice from glucose intolerance in the Duchenne muscular dystrophy (DMD) mouse model.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
He-ming Huang, Shi-jie Fan, Xiao-ru Zhou, Yan-jun Liu, Xiao Li, Li-ping Liao, Jing Huang, Cui-cui Shi, Liang Yu, Rong Fu, Jian-gao Fan, Yuan-yuan Zhang, Cheng Luo, Guang-ming Li
Summary: Givinostat demonstrated therapeutic potential in treating nonalcoholic steatohepatitis (NASH) by alleviating inflammation and attenuating hepatic fibrosis, as shown in both in vivo and in vitro studies.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Multidisciplinary Sciences
Michael Ziemba, Molly Barkhouse, Kitipong Uaesoontrachoon, Mamta Giri, Yetrib Hathout, Utkarsh J. Dang, Heather Gordish-Dressman, Kanneboyina Nagaraju, Eric P. Hoffman
Summary: Duchenne muscular dystrophy is caused by dystrophin deficiency, leading to downstream pathophysiological pathways that drive disability. Dystrophin replacement strategies may trigger these pathways, so combination therapies targeting multiple downstream pathways are crucial. Blood biomarkers could be used to assess drug combinations for treating DMD in both mouse models and human studies.
Article
Biochemistry & Molecular Biology
Yusuke Kawamura, Tetsuro Hida, Bisei Ohkawara, Masaki Matsushita, Takeshi Kobayashi, Shinya Ishizuka, Hideki Hiraiwa, Satoshi Tanaka, Mikito Tsushima, Hiroaki Nakashima, Kenyu Ito, Shiro Imagama, Mikako Ito, Akio Masuda, Naoki Ishiguro, Kinji Ohno
Summary: The anti-histamine drug meclozine promotes the proliferation and survival of human myogenic progenitor cells but inhibits myotube formation. In a mouse model of muscular dystrophy, meclozine improves muscle mass, exercise performance, and reduces ERK1/2 phosphorylation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Matteo Giovarelli, Francesca Arnaboldi, Silvia Zecchini, Laura Brigida Cornaghi, Ambra Nava, Michele Sommariva, Emilio Giuseppe Ignazio Clementi, Nicoletta Gagliano
Summary: This study provides a comprehensive histological and molecular characterization of muscle fibrosis in Duchenne muscular dystrophy (DMD), showing that fibrosis mainly affects the diaphragm and quadriceps with higher collagen cross-linking and inhibition of MMPs. These findings may lead to new targeted therapeutic interventions for DMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Neurosciences
Ken D. O'Halloran, Michael N. Maxwell, Anthony L. Marullo, Chantelle P. Hamilton, Sean C. Murchu, David P. Burns, Conor M. Mahony, Aoife D. Slyne, Sarah E. Drummond
Summary: Despite diaphragm weakness, peak inspiratory performance is preserved in young dystrophin-deficient mdx mice due to compensation by extra-diaphragmatic muscles. However, loss of compensation in advanced dystrophic disease leads to compromised respiratory system function.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Biochemistry & Molecular Biology
Keryn G. Woodman, Chantal A. Coles, Shireen R. Lamande, Jason D. White
Summary: Resveratrol at a lower dosage showed potential efficacy in reducing muscle damage and inflammatory cell markers associated with Duchenne muscular dystrophy, suggesting it as a candidate drug for treating DMD.
Article
Biochemistry & Molecular Biology
Nathalie Bourg, Ai Vu Hong, William Lostal, Abbass Jaber, Nicolas Guerchet, Guillaume Tanniou, Fanny Bordier, Emilie Bertil-Froidevaux, Christophe Georger, Nathalie Daniele, Isabelle Richard, David Israeli
Summary: Duchenne muscular dystrophy (DMD) is a common and incurable muscle genetic disease, and therapeutic approaches have focused on restoring dystrophin expression. However, the efficacy of this treatment is still unsatisfactory, potentially due to unresolved technical issues and the progressive nature of DMD. Recent research has identified abnormalities in the mevalonate pathway and cholesterol metabolism in DMD patients, which can be improved by simvastatin treatment. This study investigated the additive beneficial effect of dystrophin restoration and simvastatin treatment, but no additional benefit was observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell Biology
Laetitia Marcadet, Emma Sara Juracic, Nasrin Khan, Zineb Bouredji, Hideo Yagita, Leanne M. Ward, A. Russell Tupling, Anteneh Argaw, Jerome Frenette
Summary: Cardiomyopathy is a leading cause of death in DMD patients. Inhibition of RANKL-RANK interaction improves muscle and bone functions in mdx mice. Anti-RANKL treatment prevents cardiac hypertrophy and dysfunction by inhibiting NF-κB and PI3K pathways.
Editorial Material
Cell Biology
Chiara Mozzetta, Francesco Saverio Tedesco
JOURNAL OF CELL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Angela Cirigliano, Antonia Amelina, Beatrice Biferali, Alberto Macone, Chiara Mozzetta, Michele Maria Bianchi, Mattia Mori, Bruno Botta, Elah Pick, Rodolfo Negri, Teresa Rinaldi
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
(2020)
Article
Biochemistry & Molecular Biology
Piera Filomena Fiore, Anna Benedetti, Martina Sandona, Luca Madaro, Marco De Bardi, Valentina Saccone, Pier Lorenzo Puri, Cesare Gargioli, Biliana Lozanoska-Ochser, Marina Bouche
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2020)
Editorial Material
Cell Biology
Fulvio Chiacchiera, Lluis Morey, Chiara Mozzetta
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2020)
Article
Medicine, Research & Experimental
Andrea Bianchi, Chiara Mozzetta, Gloria Pegoli, Federica Lucini, Sara Valsoni, Valentina Rosti, Cristiano Petrini, Alice Cortesi, Francesco Gregoretti, Laura Antonelli, Gennaro Oliva, Marco De Bardi, Roberto Rizzi, Beatrice Bodega, Diego Pasini, Francesco Ferrari, Claudia Bearzi, Chiara Lanzuolo
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Biochemistry & Molecular Biology
Martina Sandona, Silvia Consalvi, Luca Tucciarone, Marco De Bardi, Manuel Scimeca, Daniela Francesca Angelini, Valentina Buffa, Adele D'Amico, Enrico Silvio Bertini, Sara Cazzaniga, Paolo Bettica, Marina Bouche, Antonella Bongiovanni, Pier Lorenzo Puri, Valentina Saccone
Article
Multidisciplinary Sciences
Gloria Pegoli, Federica Lucini, Chiara Mozzetta, Chiara Lanzuolo
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2020)
Article
Biology
Andrea Cipriano, Martina Macino, Giulia Buonaiuto, Tiziana Santini, Beatrice Biferali, Giovanna Peruzzi, Alessio Colantoni, Chiara Mozzetta, Monica Ballarino
Summary: This study identified a novel lncRNA, Lnc-Rewind, which regulates MuSC proliferation and expansion by influencing the expression of skeletal muscle genes and components of the WNT signaling pathway in mouse. The interaction of Lnc-Rewind with the G9a histone lysine methyltransferase mediates the repression of the Wnt7b gene, providing insights into the epigenetic regulation of adult muscle stem cells fate by lncRNAs.
Review
Biotechnology & Applied Microbiology
Martina Sandona, Lorena Di Pietro, Federica Esposito, Alessia Ventura, Antonietta Rosa Silini, Ornella Parolini, Valentina Saccone
Summary: Mesenchymal stromal cells (MSCs) are multipotent cells found in various tissues that have anti-fibrotic and immunoregulatory properties. Their secretome, including extracellular vesicles (EVs), can mimic the therapeutic effects of MSCs and offer advantages such as easier storage and safer administration for muscle regeneration in different diseases.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2021)
Article
Multidisciplinary Sciences
Beatrice Biferali, Valeria Bianconi, Daniel Fernandez Perez, Sophie Poehle Kronawitter, Fabrizia Marullo, Roberta Maggio, Tiziana Santini, Federica Polverino, Stefano Biagioni, Vincenzo Summa, Carlo Toniatti, Diego Pasini, Sigmar Stricker, Romano Di Fabio, Fulvio Chiacchiera, Giovanna Peruzzi, Chiara Mozzetta
Summary: The study identified Prdm16 as a nuclear envelope protein that anchors H3K9-methylated chromatin in a cell-specific manner and regulates developmental capacities of fibro-adipogenic progenitors (FAPs). Prdm16 orchestrates lamina-associated domain organization and heterochromatin sequestration at the nuclear periphery, affecting gene expression and cell fate in FAPs.
Review
Genetics & Heredity
Valeria Bianconi, Chiara Mozzetta
Summary: Muscle stem cells (MuSCs) undergo fate decisions regulated by chromatin-modifying enzymes and myogenic transcription factors. Chromatin topology plays a role in shaping the 3D genome architecture of MuSCs and maintaining cell identity. Defects in epigenetic control contribute to the pathogenesis of muscle diseases.
TRENDS IN GENETICS
(2022)
Article
Biology
Marta Morotti, Stefano Garofalo, Germana Cocozza, Fabrizio Antonangeli, Valeria Bianconi, Chiara Mozzetta, Maria Egle De Stefano, Riccardo Capitani, Heike Wulff, Cristina Limatola, Myriam Catalano, Francesca Grassi
Summary: In Duchenne muscular dystrophy, the calcium-activated potassium channel K(Ca)3.1 plays a crucial role in controlling macrophage and fibroblast function. Blockade of this channel with drugs promotes an anti-inflammatory phenotype in tissue macrophages and reduces muscle damage.
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)
Article
Multidisciplinary Sciences
Dario Dattilo, Gaia Di Timoteo, Adriano Setti, Andrea Giuliani, Giovanna Peruzzi, Manuel Beltran Nebot, Alvaro Centron-Broco, Davide Mariani, Chiara Mozzetta, Irene Bozzoni
Summary: The study identifies m(6)A machinery and the RNA helicase DDX5 as factors responsible for the increase of a subset of circRNAs in RMS, providing protein and RNA candidates for the study of its tumorigenicity.
NATURE COMMUNICATIONS
(2023)
Article
Biology
Martina Macino, Beatrice Biferali, Andrea Cipriano, Monica Ballarino, Chiara Mozzetta
Summary: In this study, a protocol for isolating viable single myofibers from the EDL skeletal muscle of adult mice and manipulating the expression of lncRNAs through antisense LNA GapmeRs-mediated knock-down (KD) was detailed. The EdU incorporation method, combined with lncRNA KD and subsequent immunofluorescence analysis, allows for the inference of lncRNAs function on muscle stem cells dynamics.