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
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.
Review
Cell Biology
Tue L. Nielsen, John Vissing, Thomas O. Krag
Summary: While preclinical studies have shown potential for increasing muscle mass and improving the pathological features of muscle diseases by inhibiting myostatin, there has been a lack of successful translation of these results into clinical trials with patient populations.
Article
Pharmacology & Pharmacy
Zeren Sun, Dengqiu Xu, Lei Zhao, Xihua Li, Sijia Li, Xiaofei Huang, Chunjie Li, Lixin Sun, Bing Liu, Zhenzhou Jiang, Luyong Zhang
Summary: The study found that fenofibrate can promote the differentiation of myofibers by down-regulating the expression of myostatin protein in myoblasts, significantly improving muscle function and reducing muscle damage in mdx mice, along with anti-inflammatory effects.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Maja Arendt, Aime Ambrosen, Tove Fall, Marcin Kierczak, Katarina Tengvall, Jennifer R. S. Meadows, Asa Karlsson, Anne-Sofie Lagerstedt, Tomas Bergstrom, Goran Andersson, Kerstin Lindblad-Toh, Ragnvi Hagman
Summary: A genome-wide association study in golden retrievers identified a genetic risk locus on chromosome 22 within the ABCC4 gene associated with pyometra, and missense SNPs within this gene may play a potential role in disease development. Another locus on chromosome 18 overlapping the TESMIN gene is also potentially implicated in the disease development.
SCIENTIFIC REPORTS
(2021)
Article
Multidisciplinary Sciences
Hiroyasu Muramatsu, Taichi Kuramochi, Hitoshi Katada, Atsunori Ueyama, Yoshinao Ruike, Ken Ohmine, Meiri Shida-Kawazoe, Rie Miyano-Nishizawa, Yuichiro Shimizu, Momoko Okuda, Yuji Hori, Madoka Hayashi, Kenta Haraya, Nobuhiro Ban, Tatsuya Nonaka, Masaki Honda, Hidetomo Kitamura, Kunihiro Hattori, Takehisa Kitazawa, Tomoyuki Igawa, Yoshiki Kawabe, Junichi Nezu
Summary: This study introduces a novel antibody therapeutic approach targeting myostatin, which shows superior muscle strength-improvement effects in mouse disease models and normal cynomolgus monkeys. The effectiveness of GYM329 is attributed to its myostatin specificity and sweeping capability, indicating its potential in improving muscle strength in patients with muscular disorders.
SCIENTIFIC REPORTS
(2021)
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
Cell Biology
Deborah Cardoso, Ines Barthelemy, Stephane Blot, Antoine Muchir
Summary: Duchenne muscular dystrophy is a disease caused by mutations in the DMD gene, leading to muscle atrophy. Current treatments only provide palliative benefits. Animal models have been instrumental in studying the disease and developing treatment strategies. Recent studies suggest that increasing NAD(+) content can mitigate muscle disease.
Article
Immunology
Laura Yedigaryan, Ester Martinez-Sarra, Giorgia Giacomazzi, Nefele Giarratana, Bernard K. van der Veer, Alessio Rotini, Silvia Querceto, Hanne Grosemans, Alvaro Cortes-Calabuig, Sara Salucci, Michela Battistelli, Elisabetta Falcieri, Rik Gijsbers, Mattia Quattrocelli, Kian Peng Koh, Liesbeth De Waele, Gunnar M. Buyse, Rita Derua, Maurilio Sampaolesi
Summary: This study identifies an extracellular vesicle-derived miRNA signature that enhances the myogenic potential of myogenic stem cells, leading to improvements in muscle degeneration and muscle wasting related diseases.
FRONTIERS IN IMMUNOLOGY
(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.
Article
Geriatrics & Gerontology
Dengqiu Xu, Sijia Li, Lu Wang, Jingwei Jiang, Lei Zhao, Xiaofei Huang, Zeren Sun, Chunjie Li, Lixin Sun, Xihua Li, Zhenzhou Jiang, Luyong Zhang
Summary: This study found that TAK1 activation worsens fibrosis and muscle degeneration, while TAK1 inhibition can improve muscle quality and function, providing a potential new therapeutic approach for DMD.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2021)
Article
Multidisciplinary Sciences
Marco Thurkauf, Shuo Lin, Filippo Oliveri, Dirk Grimm, Randall J. Platt, Markus A. Ruegg
Summary: This study establishes a highly efficient somatic gene deletion system by combining Cre-mediated skeletal muscle fiber-specific Cas9 expression with myotropic adeno-associated virus-mediated sgRNA delivery. Using this system, specific genes can be locally or systemically inactivated, replicating the phenotype of traditional gene-knockout mouse models and unraveling the function of individual genes or entire signaling pathways in adult skeletal muscle fibers.
NATURE COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Dong Kyung Sung, Hyeongseop Kim, Sang Eon Park, Jiwon Lee, Ju-A Kim, Young-Chul Park, Hong Bae Jeon, Jong Wook Chang, Jeehun Lee
Summary: This study demonstrated that oral administration of Lactobacillus casei expressing modified human myostatin (BLS-M22) can stimulate the production of sufficient myostatin-specific antibodies and improve the dystrophic features of a mouse model of Duchenne muscular dystrophy (mdx mouse). BLS-M22 treatment resulted in significantly increased levels of anti-myostatin IgG and decreased serum creatine kinase levels in mdx mice. It also improved body weight, motor function, and histological characteristics. The circulating antibodies generated after BLS-M22 administration successfully decreased serum myostatin concentration. Overall, the findings suggest the potential of BLS-M22 as a treatment for DMD, but further clinical trials are necessary to determine its efficacy and safety in humans.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Clinical Neurology
Ursula Moore, Esther Fernandez-Simon, Marianela Schiava, Dan Cox, Heather Gordish-Dressman, Meredith K. James, Anna Mayhew, Ian Wilson, Michela Guglieri, Laura Rufibach, Andrew Blamire, Pierre G. Carlier, Madoka Mori-Yoshimura, John W. Day, Kristi J. Jones, Diana X. Bharucha-Goebel, Emmanuelle Salort-Campana, Alan Pestronk, Maggie C. Walter, Carmen Paradas, Tanya Stojkovic, Elena Bravver, Elena Pegoraro, Jerry R. Mendell, Kate Bushby, Jordi Diaz-Manera, Volker Straub
Summary: This study assessed the roles of serum myostatin and follistatin concentrations in dysferlinopathy as monitoring or prognostic biomarkers. The results showed that myostatin correlated with muscle function and MRI measurements, while its changes over three years did not correlate with functional or MRI changes. Linear modeling demonstrated that function, serum creatine kinase, and C-reactive protein were independently related to myostatin concentration. Baseline myostatin concentration predicted loss of ambulation, but not the rate of change in functional or MRI measures. Overall, myostatin does not appear to be a promising treatment target in dysferlinopathy.
NEUROMUSCULAR DISORDERS
(2023)
Article
Clinical Neurology
Jan Brands, Frank Steffen, Jochen Spennes, Tosso Leeb, Thomas Bilzer
Summary: This study describes analogous clinical signs and histopathological alterations in Landseer dogs, showing that these affected dogs can serve as a valuable animal model for human Ullrich congenital 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
Computer Science, Interdisciplinary Applications
Jiazhou Chen, Guoqiang Han, Hongmin Cai, Defu Yang, Paul J. Laurienti, Martin Styner, Guorong Wu
Summary: The spatial patterns of disease-relevant brain alterations follow large-scale brain networks rather than occurring randomly. A novel connectome harmonic analysis framework is proposed to provide enhanced mathematical insights into disease progression by detecting frequency-based alterations relevant to brain disorders. This approach outperforms Euclidean methods in identifying significant and reproducible network dysfunction patterns related to Alzheimer's disease.
IEEE TRANSACTIONS ON MEDICAL IMAGING
(2021)
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
Endocrinology & Metabolism
Rebecca C. Knickmeyer, Crystal T. Nguyen, Jeffrey T. Young, Anne Haunton, Michael R. Kosorok, John H. Gilmore, Martin Styner, Debora A. Rothmond, Pamela L. Noble, Rhoshel Lenroot, Cynthia Shannon Weickert
Summary: The study found that prepubertal gonadectomy alters the developmental trajectory of prefrontal gray matter in male rhesus macaques, suggesting that the prefrontal cortex is more vulnerable to gonadectomy compared to other brain regions.
PSYCHONEUROENDOCRINOLOGY
(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
Danielle N. Rendina, Gabriele R. Lubach, Mark Lyte, Gregory J. Phillips, Ankush Gosain, Joseph F. Pierre, Roza M. Vlasova, Martin A. Styner, Christopher L. Coe
Summary: This study tracked the assembly of gut microbiota during the initial nursing period and transition to solid food in infant monkeys. The dynamic bacterial community structure reflected different maturational phases, influenced early by breast milk and later by solid foods. Higher abundance of certain microbial taxa during nursing was associated with slower growth trajectories and smaller brain volumes at one year of age.
Article
Multidisciplinary Sciences
Alexander L. Carlson, Kai Xia, M. Andrea Azcarate-Peril, Samuel P. Rosin, Jason P. Fine, Wancen Mu, Jared B. Zopp, Mary C. Kimmel, Martin A. Styner, Amanda L. Thompson, Cathi B. Propper, Rebecca C. Knickmeyer
Summary: Experimental manipulation of the gut microbiome in animal models impacts fear behaviors. This pilot study suggests associations between features of the human infant gut microbiome and non-social fear behaviors. Understanding the role of the gut microbiome in human fear behavior development requires further validation with a larger sample size.
NATURE COMMUNICATIONS
(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
Genetics & Heredity
Kai Xia, Andrey A. Shabalin, Zhaoyu Yin, Wonil Chung, Patrick F. Sullivan, Fred A. Wright, Martin Styner, John H. Gilmore, Rebecca C. Santelli, Fei Zou
Summary: We developed an efficient alternative called TwinEQTL to the linear mixed-effects model for twin genome-wide association study data. TwinEQTL splits twin samples into two independent groups and combines the test results using a meta-analysis-like approach. Mathematical derivations and simulations show that TwinEQTL is valid and has comparable power to the gold-standard linear mixed-effects models.
Article
Cell Biology
Sharla M. Birch, Michael W. Lawlor, Thomas J. Conlon, Lee-Jae Guo, Julie M. Crudele, Eleanor C. Hawkins, Peter P. Nghiem, Mihye Ahn, Hui Meng, Margaret J. Beatka, Brittany A. Fickau, Juan C. Prieto, Martin A. Styner, Michael J. Struharik, Courtney Shanks, Kristy J. Brown, Diane Golebiowski, Amanda K. Bettis, Cynthia J. Balog-Alvarez, Nathalie Clement, Kirsten E. Coleman, Manuela Corti, Xiufang Pan, Stephen D. Hauschka, J. Patrick Gonzalez, Carl A. Morris, Joel S. Schneider, Dongsheng Duan, Jeffrey S. Chamberlain, Barry J. Byrne, Joe. N. Kornegay
Summary: Duchenne muscular dystrophy (DMD) is a progressive muscle wasting disease caused by the absence of dystrophin. This study evaluated the clinical translatability of an adeno-associated virus serotype 9 vector (AAV9)-microdystrophin (mu Dys5) construct in a dystrophin-deficient golden retriever muscular dystrophy (GRMD) dog model. The results showed dose-dependent increases in tissue vector genome copy numbers and mu Dys5 protein, improvement in muscle function, and reduction of histopathologic lesions. Systemically administered AAV-microdystrophin was well tolerated and could potentially provide therapeutic benefit for DMD patients.
SCIENCE TRANSLATIONAL MEDICINE
(2023)