Article
Veterinary Sciences
Sarah M. Schneider, Garett T. Sansom, Lee-Jae Guo, Shinji Furuya, Brad R. Weeks, Joe N. Kornegay
Summary: This study systematically assessed cardiac lesions in carrier dogs, GRMD dogs, and normal dogs, and found that quantitative analysis of the cross-sectional area of fibrosis can distinguish the health status of different groups of dogs. The features identified in GRMD dogs are compatible with those of DMD, validating GRMD as an effective model for studying cardiomyopathy.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Review
Clinical Neurology
Mengyuan Chang, Yong Cai, Zihui Gao, Xin Chen, Boya Liu, Cheng Zhang, Weiran Yu, Qianqian Cao, Yuntian Shen, Xinlei Yao, Xiaoyang Chen, Hualin Sun
Summary: Duchenne muscular dystrophy (DMD) is a severe and progressive muscle-wasting disease, characterized by deterioration of skeletal muscle and loss of mobility. The failure of respiratory and cardiac muscles is the main cause of premature death in most DMD patients. Dystrophin deficiency, caused by mutations in the dystrophin gene, plays a crucial role in the pathogenesis of DMD, leading to muscle cell damage and dysfunction.
JOURNAL OF NEUROLOGY
(2023)
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
Multidisciplinary Sciences
Ziad Al Tanoury, John F. Zimmerman, Jyoti Rao, Daniel Sieiro, Harold M. McNamara, Thomas Cherrier, Alejandra Rodriguez-delaRosa, Aurore Hick-Colin, Fanny Bousson, Charlotte Fugier-Schmucker, Fabio Marchiano, Bianca Habermann, Jerome Chal, Alexander P. Nesmith, Svetlana Gapon, Erica Wagner, Vandana A. Gupta, Rhonda Bassel-Duby, Eric N. Olson, Adam E. Cohen, Kevin Kit Parker, Oliver Pourquie
Summary: This study introduces an in vitro human model to investigate the pathology of Duchenne muscular dystrophy (DMD) and test new therapeutic approaches. The researchers describe an optimized protocol for differentiating human induced pluripotent stem cells (iPSC) to a late myogenic stage, which allows them to replicate classic DMD phenotypes in isogenic DMD-mutant iPSC lines. Treatment with prednisolone significantly improves muscle function in DMD iPSC lines, challenging the prevailing view that its benefits are solely due to anti-inflammatory properties.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Clinical Neurology
Kate Maresh, Andriani Papageorgiou, Deborah Ridout, Neil A. Harrison, William Mandy, David Skuse, Francesco Muntoni
Summary: Duchenne muscular dystrophy (DMD) patients, in addition to muscle loss, also experience intellectual disability and neurobehavioral co-morbidities. This study shows that boys with DMD exhibit increased startle responses to threat, similar to a DMD mouse model, and these responses normalize with dystrophin restoration.
Article
Cell Biology
Jerry R. Mendell, Perry B. Shieh, Craig M. McDonald, Zarife Sahenk, Kelly J. Lehman, Linda P. Lowes, Natalie F. Reash, Megan A. Iammarino, Lindsay N. Alfano, Brenna Sabo, Jeremy D. Woods, Christy L. Skura, Howard C. Mao, Loretta A. Staudt, Danielle A. Griffin, Sarah Lewis, Shufang Wang, Rachael A. Potter, Teji Singh, Louise R. Rodino-Klapac
Summary: Delandistrogene moxeparvovec (SRP-9001) is a gene transfer therapy that effectively improves SRP-9001 dystrophin expression and shows promising results in patients with Duchenne muscular dystrophy. However, differences in baseline motor function between different age groups may confound the evaluation of treatment effectiveness.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2023)
Article
Geriatrics & Gerontology
Mary Chesshyre, Deborah Ridout, Yasumasa Hashimoto, Yoko Ookubo, Silvia Torelli, Kate Maresh, Valeria Ricotti, Lianne Abbott, Vandana Ayyar Gupta, Marion Main, Giulia Ferrari, Anna Kowala, Yung-Yao Lin, Francesco Saverio Tedesco, Mariacristina Scoto, Giovanni Baranello, Adnan Manzur, Yoshitsugu Aoki, Francesco Muntoni
Summary: This study highlights the importance of considering the expected effects of DMD mutations on dystrophin isoform production when evaluating motor impairments in DMD patients. Mutations that disrupt Dp140 and Dp71 are found to have a complex relationship with motor outcomes.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2022)
Article
Biochemistry & Molecular Biology
Anna Codina, Monica Roldan, Daniel Natera-de Benito, Carlos Ortez, Robert Planas, Leslie Matalonga, Daniel Cuadras, Laura Carrera, Jesica Exposito, Jesus Marquez, Cecilia Jimenez-Mallebrera, Josep M. Porta, Andres Nascimento, Cristina Jou
Summary: We developed a method for quantifying dystrophin in DMD and BMD patients using spectral confocal microscopy. The proposed methodology correctly classified patients according to their diagnosis and automated ROI selection. Spectral imaging could be implemented to measure dystrophin expression and pave the way for detailed analysis of its relation to the clinical course. Further studies could be done to understand the expression of dystrophin-associated protein complexes (DAPCs).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Physiology
Addeli Bez Batti Angulski, Nora Hosny, Houda Cohen, Ashley A. Martin, Dongwoo Hahn, Jack Bauer, Joseph M. Metzger
Summary: Duchenne muscular dystrophy (DMD) is a severe and fatal disease characterized by muscle wasting, respiratory insufficiency, and cardiomyopathy. The dystrophin gene plays a central role in the pathogenesis of DMD, with the muscle membrane and associated proteins being key components. This review examines the pathophysiology of DMD, current therapeutic strategies, and ongoing clinical trials for the treatment of this devastating disease.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Oncology
Nancy Alnassar, Malgorzata Borczyk, Georgia Tsagkogeorga, Michal Korostynski, Namshik Han, Dariusz C. Gorecki
Summary: Mutations in the DMD gene cause Duchenne muscular dystrophy (DMD), but recent research shows that reduced DMD expression is also associated with various malignancies. The downregulation of DMD in tumors is correlated with reduced patient survival and tumor stage. These findings challenge the current understanding of dystrophin expression and suggest a broader significance of the DMD gene beyond DMD.
Review
Biochemistry & Molecular Biology
Nicolas Dubuisson, Romain Versele, Chloe Planchon, Camille M. Selvais, Laurence Noel, Michel Abou-Samra, Maria A. Davis-Lopez de Carrizosa
Summary: Duchenne muscular dystrophy (DMD) is a progressive disease caused by the loss of function of the protein dystrophin. There is currently no cure for DMD, but advances in genetic and exon-skipping therapies show promise. Histological assessment is a crucial tool for evaluating degeneration and regeneration, but it faces challenges due to the complexity of molecular events and the multitude of markers involved.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Cedric Happi Mbakam, Joel Rousseau, Yaoyao Lu, Anne Bigot, Kamel Mamchaoui, Vincent Mouly, Jacques P. Tremblay
Summary: In this study, researchers used CRISPR-Cas9 prime editing technology to correct a mutation in the DMD gene, resulting in improved editing efficiency and restoration of dystrophin protein expression. Optimization of the reverse transcription template sequence led to a significant increase in the editing percentage of the target nucleotide.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Letter
Medicine, General & Internal
Carsten G. Boennemann, Beth A. Belluscio, Serge Braun, Carl Morris, Teji Singh, Francesco Muntoni
Summary: Five boys with Duchenne's muscular dystrophy received gene therapy using three different AAV products. However, they experienced serious adverse reactions and laboratory findings indicated cytotoxic T-cell immune responses.
NEW ENGLAND JOURNAL OF MEDICINE
(2023)
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)
Review
Pharmacology & Pharmacy
Mohsan Iftikhar, Justin Frey, Md Jasimuddin Shohan, Sohail Malek, Shaker A. Mousa
Summary: Many neuromuscular diseases are genetically inherited, with two common ones being Duchenne Muscular Dystrophy and Spinal Muscular Atrophy. Patients with these diseases often require supportive therapy, nutrition, and respiratory assistance, with FDA-approved drug therapies available to treat specific types of DMD and SMA.
PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Biochemistry & Molecular Biology
Sara Mata Lopez, Cynthia Balog-Alvarez, Emily H. Canessa, Yetrib Hathout, Kristy J. Brown, Stanislav Vitha, Amanda K. Bettis, Jessica Boehler, Joe N. Kornegay, Peter P. Nghiem
Article
Cell Biology
Claire Yuan, Ashwin Arora, Anthony M. Garofalo, Robert W. Grange
Summary: This study explores the potential signaling between dystrophic skeletal muscle and tendon in Duchenne muscular dystrophy, focusing on the cross-talk at the myotendinous junction. The absence of dystrophin and the associated dystrophin-glycoprotein complex is a key feature of Duchenne muscular dystrophy, with other potential signal pathways contributing to the cross-talk between muscle and tendon.
CONNECTIVE TISSUE RESEARCH
(2021)
Article
Physiology
Katherine E. Bukovec, Xiao Hu, Matthew Borkowski, Duane Jeffery, Silvia S. Blemker, Robert W. Grange
JOURNAL OF APPLIED PHYSIOLOGY
(2020)
Article
Clinical Neurology
Eleanor C. Hawkins, Amanda K. Bettis, Joe N. Kornegay
NEUROMUSCULAR DISORDERS
(2020)
Article
Multidisciplinary Sciences
Jessica R. Terrill, Basma A. Al-Mshhdani, Marisa N. Duong, Catherine D. Wingate, Zahra Abbas, Angelo P. Baustista, Amanda K. Bettis, Cynthia J. Balog-Alvarez, Joe N. Kornegay, Peter P. Nghiem, Miranda D. Grounds, Peter G. Arthur
Review
Clinical Neurology
Lejla Alic, John F. Griffin, Aydin Eresen, Joe N. Kornegay, Jim X. Ji
Summary: There is a high demand for accurate and non-invasive measures to better understand the progression and treatment outcomes of Duchenne muscular dystrophy (DMD). MRI sequences and analysis methods, such as T1w, T2w, T2map, Dixon, and MRS, have been used to assess structural alterations of DMD muscle, leading to more precise estimation of disease severity. More longitudinal studies assessing interventions in both clinical and animal model subjects are needed to validate MRI as a biomarker in DMD.
Article
Biochemistry & Molecular Biology
Benjamin R. Pryce, Cedrik Labreche, Dounia Hamoudi, John Abou-Hamad, Khalid N. Al-Zahrani, Jonathan J. Hodgins, Antoine Boulanger-Piette, Sabrina Bosse, Cindy Balog-Alvarez, Jerome Frenette, Michele Ardolino, Joe N. Kornegay, Luc A. Sabourin
Summary: Duchenne's muscular dystrophy (DMD) is a severe muscle wasting disorder characterized by muscle necrosis and decreased function. Poor muscle regeneration due to cytokine stress, along with cardiac and respiratory dysfunction, is the primary cause of death in patients. Finding new therapeutic targets is necessary to address the limited treatment options for DMD.
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH
(2021)
Article
Physiology
Sabah N. Rezvani, Anne E. C. Nichols, Robert W. Grange, Linda A. Dahlgren, P. Gunnar Brolinson, Vincent M. Wang
Summary: Achilles tendinopathy is a challenging condition with limited effective therapies. This study introduced a novel mouse model of hindlimb muscle loading for targeted therapeutic exercise, showing promising results in improving biomechanical outcomes in a murine tendinopathy model. This model opens up possibilities for further research on how muscle loading can enhance healing of Achilles tendon injuries.
JOURNAL OF APPLIED PHYSIOLOGY
(2021)
Article
Medicine, Research & Experimental
Shelby E. Hamm, Daniel D. Fathalikhani, Katherine E. Bukovec, Adele K. Addington, Haiyan Zhang, Justin B. Perry, Ryan P. McMillan, Michael W. Lawlor, Mariah J. Prom, Mark A. Vanden Avond, Suresh N. Kumar, Kirsten E. Coleman, J. B. Dupont, David L. Mack, David A. Brown, Carl A. Morris, J. Patrick Gonzalez, Robert W. Grange
Summary: The study showed that combining voluntary wheel running with microdystrophin gene therapy in young mdx mice improved whole-body performance, affected muscle function to varying degrees, mitigated energy deficits, but also revealed some detrimental effects of exercise.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Multidisciplinary Sciences
Paul T. Martin, Deborah A. Zygmunt, Anna Ashbrook, Sonia Hamilton, Davin Packer, Sharla M. Birch, Amanda K. Bettis, Cynthia J. Balog-Alvarez, Lee-Jae Guo, Peter P. Nghiem, Joe N. Kornegay
Summary: Short-term intravenous treatment of GRMD dogs with rAAVrh74.MHCK7.GALGT2 at high doses can induce muscle glycosylation and utrophin expression over a short 3-month interval, showing modest effects on muscle pathology and no significant improvement on muscle strength. Serum chemistry, hematology, and cardiac function measures were largely unchanged by treatment.
Article
Biochemistry & Molecular Biology
Yusuke Echigoya, Nhu Trieu, William Duddy, Hong M. Moulton, HaiFang Yin, Terence A. Partridge, Eric P. Hoffman, Joe N. Kornegay, Frank A. Rohret, Christopher S. Rogers, Toshifumi Yokota
Summary: Duchenne muscular dystrophy (DMD) is a lethal genetic disorder caused by mutations in the DMD gene. Although PMO-ASOs have been approved for clinical use, their applicability remains limited. Establishing a DMD large animal model is crucial for evaluating treatment efficacy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Nutrition & Dietetics
Brittney Knott, Matthew A. Kocher, Henry A. Paz, Shelby E. Hamm, William Fink, Jordan Mason, Robert W. Grange, Umesh D. Wankhade, Deborah J. Good
Summary: This study demonstrated that Snord116(m+/p-) mice and mice with a deletion of both Snord116 alleles showed weight and fat loss on a high-fat/CLA diet, indicating that the genotype did not interfere with CLA actions. There were no changes in food intake or metabolic rate, and only moderate differences in exercise performance. RNA-seq and microbiome analyses identified hypothalamic mRNAs and differentially populated gut bacteria, supporting future mechanistic analyses.
Correction
Medicine, Research & Experimental
Shelby E. Hamm, Daniel D. Fathalikhani, Katherine E. Bukovec, Adele K. Addington, Haiyan Zhang, Justin B. Perry, Ryan P. McMillan, Michael W. Lawlor, Mariah J. Prom, Mark A. Vanden Avond, Suresh N. Kumar, Kirsten E. Coleman, J. B. Dupont, David L. Mack, David A. Brown, Carl A. Morris, J. Patrick Gonzalez, Robert W. Grange
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Veterinary Sciences
Sarah M. Schneider, Garett T. Sansom, Lee-Jae Guo, Shinji Furuya, Brad R. Weeks, Joe N. Kornegay
Summary: This study systematically assessed cardiac lesions in carrier dogs, GRMD dogs, and normal dogs, and found that quantitative analysis of the cross-sectional area of fibrosis can distinguish the health status of different groups of dogs. The features identified in GRMD dogs are compatible with those of DMD, validating GRMD as an effective model for studying cardiomyopathy.
FRONTIERS IN VETERINARY SCIENCE
(2022)
Article
Education, Scientific Disciplines
R. Mark Simpson, Shelley B. Hoover, Barbara J. Davis, John Hickerson, Margaret A. Miller, Matti Kiupel, John M. Cullen, Jennifer E. Dwyer, Bih-Rong Wei, Thomas J. Rosol, Joe N. Kornegay, Siba K. Samal
JOURNAL OF VETERINARY MEDICAL EDUCATION
(2020)
