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
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
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
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
Biology
Juliana Marulanda, Iris Boraschi-Diaz, Pierre Beauparlant, Philippe Crine, Frank Rauch
Summary: The study demonstrated that treatment with a bone-targeted TGFbeta antibody (PCT-011) significantly improved bone development in mdx mice, suggesting that inhibiting TGFbeta activity could be a promising approach to treating bone fragility in the context of DMD.
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
Michael Stirm, Bachuki Shashikadze, Andreas Blutke, Elisabeth Kemter, Andreas Lange, Jan B. Stoeckl, Florian Jaudas, Laeticia Laane, Mayuko Kurome, Barbara Kessler, Valeri Zakhartchenko, Andrea Baehr, Nikolai Klymiuk, Hiroshi Nagashima, Maggie C. Walter, Wolfgang Wurst, Christian Kupatt, Thomas Froehlich, Eckhard Wolf
Summary: Skipping DMD exon 51 can restore dystrophin expression and improve cardiac function in DMD patients and animal models.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
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
Biochemistry & Molecular Biology
Rebeca Acin-Perez, Cristiane Beninca, Lucia Fernandez del Rio, Cynthia Shu, Siyouneh Baghdasarian, Vanessa Zanette, Christoph Gerle, Chimari Jiko, Ramzi Khairallah, Shaharyar Khan, David Rincon Fernandez Pacheco, Byourak Shabane, Karel Erion, Ruchi Masand, Sundeep Dugar, Cristina Ghenoiu, George Schreiner, Linsey Stiles, Marc Liesa, Orian S. Shirihai
Summary: The regulation of ATP synthesis and hydrolysis is crucial for cellular function. In this study, we investigate the hydrolytic activity of mitochondrial ATP synthase (CV) and its impact on cellular energetics. We identify a selective inhibitor of ATP hydrolysis, (+)-Epicatechin, that binds CV and prevents the binding of ATPase inhibitor (ATPIF1). By inhibiting CV hydrolytic activity, ATP content is restored in cells with respiratory chain defects or Duchenne Muscular Dystrophy, improving muscle force without increasing mitochondrial content. These findings highlight the potential of hydrolysis-selective inhibitors of CV in mitigating the effects of compromised mitochondrial respiration.
Review
Biotechnology & Applied Microbiology
Lam Chung Liang, Nadiah Sulaiman, Muhammad Dain Yazid
Summary: Duchenne muscular dystrophy (DMD) is a severe form of muscle dystrophy that currently lacks effective treatment options. Gene therapy has been proposed as a potential solution, but it also faces limitations and challenges.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2022)
Article
Medicine, General & Internal
Taylor Gould, Takako Jones, Peter L. Jones
Summary: The true prevalence of facioscapulohumeral muscular dystrophy (FSHD) remains unknown, but epigenetic analysis could provide a diagnostic pathway for sequence-based diagnosis. Conflicting results from studies assessing DNA methylation at the FSHD locus have made the utility of this technique controversial for FSHD diagnosis.
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)
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
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
Engineering, Biomedical
Aydin Eresen, Sharla M. Birch, Lejla Alic, John F. Griffin, Joe N. Kornegay, Jim Xiuquan Ji
IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING
(2019)
Article
Clinical Neurology
Aydin Eresen, Lejla Alic, Sharla M. Birch, Wade Friedeck, John F. Griffin, Joe N. Kornegay, Jim X. Ji
Article
Biochemistry & Molecular Biology
Pamela Barraza-Flores, Tatiana M. Fontelonga, Ryan D. Wuebbles, Hailey J. Hermann, Andreia M. Nunes, Joe N. Kornegay, Dean J. Burkin
HUMAN MOLECULAR GENETICS
(2019)
Article
Cardiac & Cardiovascular Systems
Lee-Jae Guo, Jonathan H. Soslow, Amanda K. Bettis, Peter P. Nghiem, Kevin J. Cummings, Mark W. Lenox, Matthew W. Miller, Joe N. Kornegay, Christopher F. Spurney
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2019)
Article
Biochemistry & Molecular Biology
Yafeng Song, Leon Morales, Alock S. Malik, Andrew F. Mead, Christopher D. Greer, Marilyn A. Mitchell, Mihail T. Petrov, Leonard T. Su, Margaret E. Choi, Shira T. Rosenblum, Xiangping Lu, Daniel J. VanBelzen, Ranjith K. Krishnankutty, Frederick J. Balzer, Emanuele Loro, Robert French, Kathleen J. Propert, Shangzhen Zhou, Benjamin W. Kozyak, Peter P. Nghiem, Tejvir S. Khurana, Joe N. Kornegay, Hansell H. Stedman
Article
Multidisciplinary Sciences
Sara Mata Lopez, Cynthia Balog-Alvarez, Stanislav Vitha, Amanda K. Bettis, Emily H. Canessa, Joe N. Kornegay, Peter P. Nghiem
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
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
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
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)