Review
Cell Biology
Shanshan Yao, Zihao Chen, Yuanyuan Yu, Ning Zhang, Hewen Jiang, Ge Zhang, Zongkang Zhang, Baoting Zhang
Summary: Duchenne muscular dystrophy is a lethal neuromuscular disorder caused by the absence of dystrophin protein, with no cure currently available. The standard of care involves glucocorticoids treatments for symptom relief. Therapeutic strategies focus on restoring dystrophin function and targeting downstream pathological changes like inflammation and fibrosis.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Multidisciplinary Sciences
Michael J. Stec, Qi Su, Christina Adler, Lance Zhang, David R. Golann, Naveen P. Khan, Lampros Panagis, S. Armando Villalta, Min Ni, Yi Wei, Johnathon R. Walls, Andrew J. Murphy, George D. Yancopoulos, Gurinder S. Atwal, Sandra Kleiner, Gabor Halasz, Mark W. Sleeman
Summary: Using spatial transcriptomics and single-cell RNA sequencing datasets, a high-resolution cellular and molecular spatial atlas of the severely dystrophic D2-mdx mouse model was generated. Clustering analysis revealed the nonuniform distribution of unique cell populations associated with multiple regenerative timepoints, faithfully recapitulating the asynchronous regeneration observed in human DMD muscle. Through spatiotemporal gene expression signatures, it was found that propagation of inflammatory and fibrotic signals from locally damaged areas contributes to widespread pathology and identifying targetable pathways for DMD therapy within discrete microenvironments. Overall, this spatial atlas of dystrophic muscle provides a valuable resource for studying DMD disease biology and therapeutic target discovery.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Medicine, Research & Experimental
Francesca Florio, Sara Vencato, Filomena T. Papa, Michela Libergoli, Eyemen Kheir, Imen Ghzaiel, Thomas A. Rando, Yvan Torrente, Stefano Biressi
Summary: Fibrosis in Duchenne muscular dystrophy (DMD) is caused by the crosstalk between the complement and the WNT signaling pathways, as well as the functional interactions of fibro-adipogenic progenitors and macrophages. Inhibiting the C1r/s subunits can reduce WNT signaling activation and mitigate fibrogenic characteristics, providing new insights into therapeutic strategies for muscular dystrophy fibrosis.
EMBO MOLECULAR MEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Sharon Mordechay, Shaun Smullen, Paul Evans, Olga Genin, Mark Pines, Orna Halevy
Summary: The study showed that the enantiomers of halofuginone had differential effects on motor coordination and muscle histopathology in mdx mice, with (+)-halofuginone being the most effective. These findings suggest a potential use for (+)-halofuginone as a therapy for DMD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Silvia Consalvi, Luca Tucciarone, Elisa Macri, Marco De Bardi, Mario Picozza, Illari Salvatori, Alessandra Renzini, Sergio Valente, Antonello Mai, Viviana Moresi, Pier Lorenzo Puri
Summary: Late-stage mdx FAPs exhibit abnormal HDAC activity and genome-wide alterations of histone acetylation that cannot be fully reversed by HDACi. HDACi show general resistance in inducing H3K9/14 hyperacetylation in late-stage mdx FAPs, but is effective in reducing promoter acetylation and blunting SASP gene activation.
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
Cell Biology
Nicolas Dubuisson, Romain Versele, Maria A. Davis-Lopez de Carrizosa, Camille M. Selvais, Laurence Noel, Chloe Planchon, Peter Y. K. Van den Bergh, Sonia M. Brichard, Michel Abou-Samra
Summary: ALY688, a small peptide agonist of adiponectin receptor, shows promising therapeutic potential for Duchenne muscular dystrophy (DMD) by improving muscle function, reducing inflammation, oxidative stress, fibrosis, and myonecrosis, and enhancing myogenic program partly mediated by necroptosis. Its protective and beneficial effects are mainly mediated by the AMPK-PGC-1 alpha axis, leading to the suppression of NF-kappa beta and TGF-beta, offering a novel and effective treatment strategy for DMD.
Article
Biochemistry & Molecular Biology
Angus Lindsay, John Holm, Maria Razzoli, Alessandro Bartolomucci, James M. Ervasti, Dawn A. Lowe
Summary: Research shows that mdx mice do not habituate to mild stress, and daily exposure to mild stress for weeks exacerbates phenotypes associated with dystrophinopathy in mdx mice.
Article
Engineering, Biomedical
Kelley M. Virgilio, Brian K. Jones, Emily Y. Miller, Elnaz Ghajar-Rahimi, Kyle S. Martin, Shayn M. Peirce, Silvia S. Blemker
Summary: This study utilized an agent-based model to predict the impact of increased fibrosis on muscle regeneration, and experimentally validated the model-derived hypothesis. The findings suggest that increasing the area fraction of fibrosis alone is not enough to reduce the regenerative capacity of mdx muscle, indicating that fibrosis is a complex pathological condition that requires further understanding.
ANNALS OF BIOMEDICAL ENGINEERING
(2021)
Article
Neurosciences
Nastasia Cardone, Valentina Taglietti, Serena Baratto, Kaouthar Kefi, Baptiste Periou, Ciryl Gitiaux, Christine Barnerias, Peggy Lafuste, France Leturcq Pharm, Juliette Nectoux Pharm, Chiara Panicucci, Isabelle Desguerre, Claudio Bruno, Francois-Jerome Authier, Chiara Fiorillo, Frederic Relaix, Edoardo Malfatti
Summary: In this study, we performed myopathologic analysis on muscle biopsies from DMD patients and found an increase in fibro-adipogenic progenitors, which contribute to fibrotic progression and lipid deposition. At the same time, there was a decline in muscle regenerative capacity, which was strongly correlated with compromised activation and expansion of muscle stem cells. Additionally, our study revealed an early acquisition of a senescence phenotype by DMD-afflicted muscle stem cells. These findings highlight the importance of muscle stem cell senescence as a pivotal readout for future therapeutic interventions.
ACTA NEUROPATHOLOGICA COMMUNICATIONS
(2023)
Review
Physiology
Marine Theret, Fabio M. V. Rossi, Osvaldo Contreras
Summary: This review explores the function of fibro-adipogenic progenitors in muscle homeostatic integrity, regeneration, repair, and aging, as well as how they control the onset and severity of muscle loss in disease.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Medicine, Research & Experimental
Yan Wang, Yanfeng Xiao, Yanyan Zheng, Le Yang, Dong Wang
Summary: In this study, it was found that ADAMTS1 levels were increased in mdx mice lacking dystrophin and DMD patients. Treatment with anti-ADAMTS1 improved muscle function, reduced muscle fibrosis, and enhanced muscle strength in mdx mice. This suggests that ADAMTS1 may be a potential target for developing new biological therapies for DMD.
Article
Biochemistry & Molecular Biology
Zsofia Onodi, Petra Lujza Szabo, Daniel Kucsera, Peter Pokreisz, Christopher Dostal, Karlheinz Hilber, Gavin Y. Oudit, Bruno K. Podesser, Peter Ferdinandy, Zoltan V. Varga, Attila Kiss
Summary: Duchenne muscular dystrophy (DMD) is a muscle wasting disease characterized by difficulty moving and premature death, mainly due to heart failure. Inflammation is thought to play a role in the disease progression, but the specific mechanisms are not well understood.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Shalini Murali Krishnan, Johannes Nordlohne, Lisa Dietz, Alexandros Vakalopoulos, Petra Haning, Elke Hartmann, Roland Seifert, Joerg Hueser, Ilka Mathar, Peter Sandner
Summary: The NO-independent sGC stimulator BAY-747 showed promise in improving skeletal muscle function in a mouse model of DMD, with effects on grip strength, running speed, and CK levels, but further studies are required to fully understand its potential therapeutic benefits.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Martina Sandona, Federica Esposito, Anna Cargnoni, Antonietta Silini, Pietro Romele, Ornella Parolini, Valentina Saccone
Summary: This study demonstrates that the secretome and extracellular vesicles derived from mesenchymal stromal cells from the amniotic membrane (hAMSCs) can promote muscle regeneration by stimulating proliferation and differentiation of muscle stem cells. It also shows that these factors can modulate the muscle stem cell niche and reduce fibrosis and muscle exhaustion. These findings suggest a potential novel treatment for Duchenne muscular dystrophy (DMD).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Engineering, Biomedical
Mariana Conceica, Laura Forcina, Oscar P. B. Wiklander, Dhanu Gupta, Joel Z. Nordin, Besarte Vrellaku, Graham McClorey, Imre Mager, Andre Gorgens, Per Lundin, Antonio Musaro, Matthew J. A. Wood, Samir E. L. Andaloussi, Thomas C. Roberts
Summary: IL6 is a key mediator of inflammation that activates target cells through classical and trans-signalling pathways. Engineered EVs expressing IL6ST decoy receptors can selectively inhibit the IL6 trans-signalling pathway, providing a potential therapeutic target for chronic inflammation.
Article
Cell Biology
Gabriella Dobrowolny, Julie Martone, Elisa Lepore, Irene Casola, Antonio Petrucci, Maurizio Inghilleri, Mariangela Morlando, Alessio Colantoni, Bianca Maria Scicchitano, Andrea Calvo, Giulia Bisogni, Adriano Chio, Mario Sabatelli, Irene Bozzoni, Antonio Musaro
Summary: Through a longitudinal study of circulating miRNAs in ALS patients, it was found that high levels of miR-206, miR-133a, and miR-151a-5p can predict slower clinical decline in patient functionality. The expression of these miRNAs showed different trends at various stages of ALS pathology, suggesting their potential as prognostic markers for the disease.
CELL DEATH DISCOVERY
(2021)
Article
Cell Biology
Laura Pelosi, Maria Grazia Berardinelli, Laura Forcina, Francesca Ascenzi, Emanuele Rizzuto, Marco Sandri, Fabrizio De Benedetti, Bianca Maria Scicchitano, Antonio Musaro
Summary: IL-6 is a pleiotropic cytokine with different and opposite effects under healthy and pathologic conditions. It can stimulate muscle growth in healthy conditions but may lead to muscle wasting in pathological conditions. Increased plasma levels of IL-6 may be associated with stunted growth and muscle wasting.
Article
Cell Biology
Irene Casola, Bianca Maria Scicchitano, Elisa Lepore, Silvia Mandillo, Elisabetta Golini, Carmine Nicoletti, Laura Barberi, Gabriella Dobrowolny, Antonio Musaro
Summary: This study analyzed the expression levels of two myomiRs in different contexts, including ALS disease and denervation models. The results showed that miR-206 and miR-133a exhibit different expression patterns in ALS disease and nerve regeneration processes, which are important for understanding the pathogenesis and treatment of ALS.
Article
Pharmacology & Pharmacy
Silvia Scaricamazza, Illari Salvatori, Susanna Amadio, Valentina Nesci, Alessio Torcinaro, Giacomo Giacovazzo, Aniello Primiano, Michela Gloriani, Niccolo Candelise, Luisa Pieroni, Jean-Philippe Loeffler, Frederique Rene, Cyril Quessada, Tesfaye W. Tefera, Hao Wang, Frederik J. Steyn, Shyuan T. Ngo, Gabriella Dobrowolny, Elisa Lepore, Andrea Urbani, Antonio Musaro, Cinzia Volonte, Elisabetta Ferraro, Roberto Coccurello, Cristiana Valle, Alberto Ferri
Summary: The therapeutic potential of the multi-target drug trimetazidine was evaluated in SOD1(G93A) mice. The results showed that trimetazidine delayed disease progression, improved motor function and metabolism, and increased overall survival of the mice.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Isabella Orienti, Monica Armida, Gabriella Dobrowolny, Rita Pepponi, Gabriella Sollazzini, Antonella Pezzola, Irene Casola, Antonio Musaro, Patrizia Popoli, Rosa Luisa Potenza
Summary: Fenretinide (FEN) shows potential in preventing and overcoming the toxicity of mutant SOD1 (mSOD1) in amyotrophic lateral sclerosis (ALS). Administration of a new nanomicellar fenretinide formulation (NanoMFen) can ameliorate disease progression in ALS, with its efficacy influenced by gender and showing better effects in female subjects.
Article
Pharmacology & Pharmacy
Nicole Zoratto, Laura Forcina, Roberto Matassa, Luciana Mosca, Giuseppe Familiari, Antonio Musaro, Maurizio Mattei, Tommasina Coviello, Chiara Di Meo, Pietro Matricardi
Summary: The study shows the activity of hyaluronan-cholesterol nanogels as ocular permeation enhancers, enhancing the penetration of drugs in the eye and improving bioavailability, particularly for treating anterior and posterior eye segment diseases.
Article
Cell & Tissue Engineering
Flavia Forconi, Ludovica Apa, Simona Pisu, Irene Casola, Antonio Musaro, Emanuele Rizzuto, Zaccaria Del Prete
Summary: This study proposes a novel technique and parameter to assess the functionality of the neuromuscular junction (NMJ) under isotonic conditions, including fatigue, providing important insights into neuronal signal transmission. This technique can be applied to other animal models to investigate muscle-nerve impairments in other neurodegenerative pathologies.
CELLULAR AND MOLECULAR BIOENGINEERING
(2022)
Review
Cell Biology
Laura Forcina, Claudio Franceschi, Antonio Musaro
Summary: IL-6 is a pleiotropic cytokine with dual and sometimes opposite actions, depending on its intensity and duration of release. It can have anti-inflammatory, antioxidant, and pro-myogenic effects at low levels but can induce pro-inflammatory, pro-oxidant, and pro-fibrotic responses at increased systemic concentrations. The role of IL-6 in aging-related diseases and its involvement in the switch from physiological aging to age-related diseases, such as chronic inflammation and oxidative stress, is not fully understood.
AGEING RESEARCH REVIEWS
(2022)
Article
Chemistry, Analytical
Ludovica Apa, Marianna Cosentino, Flavia Forconi, Antonio Musaro, Emanuele Rizzuto, Zaccaria Del Prete
Summary: This study proposed an innovative sensor for continuous monitoring of engineered muscle tissue's contractility through embedded technology. The sensor utilizes calibrated deflection of a supporting pin and a noninvasive optical method to measure its movement and returns force values. Experimental results showed that the sensor did not affect the maturation of engineered muscle tissue.
Article
Biology
Valeria Taliani, Giulia Buonaiuto, Fabio Desideri, Adriano Setti, Tiziana Santini, Silvia Galfre, Leonardo Schirone, Davide Mariani, Giacomo Frati, Valentina Valenti, Sebastiano Sciarretta, Emerald Perlas, Carmine Nicoletti, Antonio Musaro, Monica Ballarino
Summary: Long noncoding RNAs (lncRNAs) play a critical role in heart physiology and disease. We identified a lncRNA called pCharme that is associated with chromatin and is involved in myogenesis and cardiac muscle remodeling in mice. Through various molecular analyses, we found that pCharme is specifically expressed in cardiomyocytes and is important for their maturation and cardiac development. The loss of pCharme leads to delayed cardiomyocyte maturation and morphological alterations in the ventricular myocardium. This study provides valuable insights into a novel lncRNA-mediated regulatory mechanism in heart development and has implications for future theranostic applications targeting the Charme locus.
Proceedings Paper
Engineering, Biomedical
Flavia Forconi, Ludovica Apa, Marianna Cosentino, Antonio Musaro, Emanuele Rizzuto, Zaccaria Del Prete
Summary: This article introduces an innovative device for measuring the contractility of engineered skeletal muscle and evaluates the impact of moving the region of interest (ROI) on the measurement of contractile force. The experimental results demonstrate that the introduced errors by moving the ROI are always lower than 4%, and the influence of errors on the measurement is less significant for larger displacements.
2022 IEEE INTERNATIONAL SYMPOSIUM ON MEDICAL MEASUREMENTS AND APPLICATIONS (MEMEA 2022)
(2022)
