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.
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)
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
Biology
Deirdre D. Scripture-Adams, Kevin N. Chesmore, Florian Barthelemy, Richard T. Wang, Shirley Nieves-Rodriguez, Derek W. Wang, Ekaterina Mokhonova, Emilie D. Douine, Jijun Wan, Isaiah Little, Laura N. Rabichow, Stanley F. Nelson, M. Carrie Miceli
Summary: This study develops a method to isolate and sequence individual nuclei from frozen muscle, allowing for the exploration of cellular and transcriptomic mechanisms in Duchenne muscular dystrophy. The findings reveal the effects of exon skipping therapy on muscle nuclei and demonstrate partial rescue of muscle fibers, expansion of myeloid population, recovery of M2 macrophages, and repression of inflammatory fibroblasts.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Adrien Morin, Amalia Stantzou, Olga N. Petrova, John Hildyard, Thomas Tensorer, Meriem Matouk, Mina V. Petkova, Isabelle Richard, Tudor Manoliu, Aurelie Goyenvalle, Sestina Falcone, Markus Schuelke, Corinne Laplace-Builhe, Richard J. Piercy, Luis Garcia, Helge Amthor
Summary: Dystrophin is crucial for muscle health, but its spatial organization is not well understood. Studying fluorescently tagged dystrophin in mice, researchers discovered that dystrophin is compartmentalized in sarcolemmal territories. At myotendinous junctions, Dmd transcripts and dystrophin protein are enriched. Genomic correction restored separated dystrophin domains, while transcript-level correction restored dystrophin initially at junctions before extending along the entire fiber. This research suggests that widespread restoration of fiber dystrophin, especially at muscle-tendon junctions, is critical for therapeutic success in DMD.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Biochemistry & Molecular Biology
Genji Watanabe, Masahito Yamamoto, Shuichirou Taniguchi, Yuki Sugiyama, Hidetomo Hirouchi, Satoshi Ishizuka, Kei Kitamura, Toshihide Mizoguchi, Takashi Takayama, Katsuhiko Hayashi, Shinichi Abe
Summary: Tendons have inferior regenerative ability compared to muscles, but Sox9 may play a crucial role in restoring tendon functions after injury.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Endocrinology & Metabolism
Justin P. Hardee, Karen J. B. Martins, Paula M. Miotto, James G. Ryall, Stefan M. Gehrig, Boris Reljic, Timur Naim, Jin D. Chung, Jen Trieu, Kristy Swiderski, Ashleigh M. Philp, Andrew Philp, Matthew J. Watt, David A. Stroud, Rene Koopman, Gregory R. Steinberg, Gordon S. Lynch
Summary: The study demonstrates that low-frequency electrical stimulation can promote metabolic and mitochondrial remodeling in dystrophic muscles in mice, offering therapeutic potential for ameliorating dystrophic pathology and protecting against injury.
MOLECULAR METABOLISM
(2021)
Review
Biochemistry & Molecular Biology
Elena Abati, Emanuele Sclarandi, Giacomo Pietro Comi, Valeria Parente, Stefania Corti
Summary: Muscular dystrophies are a group of inherited diseases characterized by skeletal muscle degeneration and weakness, with no effective therapies currently available. Human induced pluripotent stem cells are promising tools for in vitro muscle research, used for genetic and pharmacological treatment screening.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
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)
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
Clinical Neurology
Silvia Torelli, Domenic Scaglioni, Valentina Sardone, Matthew J. Ellis, Joana Domingos, Adam Jones, Lucy Feng, Darren Chambers, Deborah M. Eastwood, France Leturcq, Rabah Ben Yaou, Andoni Urtizberea, Pascal Sabouraud, Christine Barnerias, Tanya Stojkovic, Enzo Ricci, Maud Beuvin, Gisele Bonne, Caroline A. Sewry, Tracey Willis, Richa Kulshrestha, Giorgio Tasca, Rahul Phadke, Jennifer E. Morgan, Francesco Muntoni
Summary: This study reports on dystrophin expression patterns using Western blotting and image analysis in skeletal muscle biopsies of DMD, BMD, and intermediate DMD/BMD patients. Results showed significant correlation between different methodologies and significant inter- and intradisease heterogeneity of dystrophin expression patterns in patients.
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
(2021)
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
Geriatrics & Gerontology
Christopher R. Heier, Nikki M. McCormack, Christopher B. Tully, James S. Novak, Breanne L. Newell-Stamper, Alan J. Russell, Alyson A. Fiorillo
Summary: Becker muscular dystrophy (BMD) is a genetic neuromuscular disease caused by mutations in the dystrophin gene. Unlike Duchenne muscular dystrophy, BMD is less severe. However, there is a lack of research and treatment options for BMD, partly due to the absence of a mouse model.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Article
Biochemistry & Molecular Biology
Bisei Ohkawara, Masaomi Kurokawa, Akinori Kanai, Kiyomi Imamura, Guiying Chen, Ruchen Zhang, Akio Masuda, Koichi Higashi, Hiroshi Mori, Yutaka Suzuki, Ken Kurokawa, Kinji Ohno
Summary: During embryonic development, the formation of the neuromuscular junction is regulated by a series of genes. Analysis of embryonic and neonatal mouse diaphragms reveals distinct gene expression patterns in each muscle nucleus during the formation of the neuromuscular junction. Some of these genes play important roles in the process.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Biochemistry & Molecular Biology
Xiaokai Li, Zhining Zhong, Ruowei Zhang, Jiaman Zhang, Yu Zhang, Sha Zeng, Qinjiao Du, Haoming Wang, Songling Zhang, Lu Lu, Mingzhou Li, Keren Long
Summary: In this study, a muscular dystrophy mouse model was created by Ptrf knockout, and single-nucleus RNA sequencing was used to investigate the transcriptional changes in skeletal muscle. The study revealed significant alterations in the transcriptome of different types of muscle fibers and mononuclear cells in response to muscular dystrophy, providing valuable insights into the molecular mechanisms of muscular dystrophy.
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
Veterinary Sciences
Jessica S. Fortin, Chady H. Hakim, Scott Korte, N. Nora Yang, Scott D. Fitzgerald, Gayle C. Johnson, Bruce F. Smith, Dongsheng Duan
Summary: The University of Missouri established a colony of dystrophin-deficient dogs to study the genetic and molecular basis of dystrophinopathies, focusing on a female dog with abnormal genotype and phenotype, which displayed skeletal and muscle abnormalities. This case highlighted the importance of studying dystrophinopathy in female dogs without a normal X chromosome for effective therapeutic strategies.
VETERINARY MEDICINE AND SCIENCE
(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
Oncology
Kasun Kodippili, Pamela K. Thorne, M. Harold Laughlin, Dongsheng Duan
Summary: Through studying a canine DMD model, this research found that dystrophin deficiency leads to structural remodeling of the artery and impaired vascular function, suggesting that dystrophin plays a crucial role in maintaining the structure and function of vascular endothelium and smooth muscle in large mammals. Vascular defects may contribute to DMD pathogenesis.
JOURNAL OF PATHOLOGY
(2021)
Article
Cell Biology
Chady H. Hakim, Hsiao T. Yang, Matthew J. Burke, James Teixeira, Gregory J. Jenkins, N. Nora Yang, Gang Yao, Dongsheng Duan
Summary: By studying aged dystrophin-null canines' muscle pathology and contractile properties, we established a foundation for using this model in research on experimental therapies for Duchenne muscular dystrophy, revealing an unexpected myofiber-type switch in affected dogs.
DISEASE MODELS & MECHANISMS
(2021)
Article
Biochemistry & Molecular Biology
Xiufang Pan, Yongping Yue, Maria Boftsi, Lakmini P. Wasala, Ngoc Tam Tran, Keqing Zhang, David J. Pintel, Phillip W. L. Tai, Dongsheng Duan
Summary: The study found that complete elimination of CpG motifs in the ITR does not impact the biological activity of the AAV vector. CpG-free ITRs could be valuable in engineering therapeutic AAV vectors.
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)
Letter
Cardiac & Cardiovascular Systems
Dongsheng Duan, Kevin M. Flanigan, Annemieke Aartsma-Rus
Article
Biotechnology & Applied Microbiology
Nalinda B. Wasala, Emily D. Million, Thais B. Watkins, Lakmini P. Wasala, Jin Han, Yongping Yue, Baisong Lu, Shi-jie Chen, Chady H. Hakim, Dongsheng Duan
Summary: Short-term local injection of CRISPR editing technique can restore dystrophin in DMD patients, while long-term systemic injection failed. The study found that long-term systemic injection resulted in selective loss of gRNA vector, which was not affected by the injection time and dosage. In addition, a higher dose of gRNA vector was associated with better therapeutic effects.
HUMAN GENE THERAPY
(2022)
Letter
Cardiac & Cardiovascular Systems
Janine Ebner, Xiufang Pan, Yongping Yue, Spyridon Sideromenos, Jessica Marksteiner, Xaver Koenig, Karlheinz Hilber, Dongsheng Duan
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Lakmini P. Wasala, Thais B. Watkins, Nalinda B. Wasala, Matthew J. Burke, Yongping Yue, Yi Lai, Gang Yao, Dongsheng Duan
Summary: Duchenne muscular dystrophy (DMD) is a fatal muscle disease caused by dystrophin deficiency. In this study, it was found that mu Dys with both H1 and H4 effectively localized to the muscle membrane, restored the dystrophin-associated protein complex, and improved muscle force. On the other hand, mu Dys with only H1 or without H4 did not have the same effects. Therefore, H4 is essential for mu Dys function and H1 facilitates force production. These findings will contribute to the development of next-generation mu Dys gene therapy.
HUMAN GENE THERAPY
(2023)
Article
Biotechnology & Applied Microbiology
Nalinda B. Wasala, Yongping Yue, Bryan Hu, Jin-Hong Shin, Gang Yao, Dongsheng Duan
Summary: In this study, the researchers injected the AAV mu Dys vector into mdx mice and observed significant improvements in muscle strength, exercise capacity, and cardiac function. The results suggest that AAV mu Dys therapy has the potential to provide lifelong benefits in patients with Duchenne muscular dystrophy.
HUMAN GENE THERAPY
(2023)
Review
Biotechnology & Applied Microbiology
Dongsheng Duan
Summary: This mini-review summarizes clinical findings of lethal immunotoxicity induced by high-dose systemic AAV gene therapy and calls for collaborative efforts to better understand the underlying mechanisms and develop effective prevention/treatment strategies.