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)
Article
Clinical Neurology
Craig M. Zaidman, Crystal M. Proud, Craig M. Mcdonald, Kelly J. Lehman, Natalie L. Goedeker, Stefanie Mason, Alexander P. Murphy, Maitea Guridi, Shufang Wang, Carol Reid, Eddie Darton, Christoph Wandel, Sarah Lewis, Jyoti Malhotra, Danielle A. Griffin, Rachael A. Potter, Louise R. Rodino-Klapac, Jerry R. Mendell
Summary: The study ENDEAVOR demonstrated that the commercial process delandistrogene moxeparvovec is safe and effective in improving micro-dystrophin expression in patients with Duchenne muscular dystrophy. After 12 weeks of treatment, significant improvements were observed in micro-dystrophin expression, as well as patient's functional outcomes and quality of life at 1 year.
ANNALS OF NEUROLOGY
(2023)
Article
Clinical Neurology
Giulio Gadaleta, Guido Urbano, Chiara Brusa, Rossella D'Alessandro, Enrica Rolle, Ilaria Cavallina, Alessio Mattei, Fulvia Ribolla, Claudia Raineri, Stefano Pidello, Liliana Vercelli, Federica S. Ricci, Tiziana E. Mongini
Summary: The clinical characteristics of adults with DMD include mechanical ventilation, swallowing and nutritional issues, and bone density alterations. Other issues include respiratory infections, gastrointestinal symptoms, metabolic acidosis, psychiatric symptoms, and chronic pain. Patients have a negative perception of their physical health but a more positive assessment of their mental health.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Article
Biochemistry & Molecular Biology
Alexander B. Andre, Liqiang Zhang, Jalen D. Nix, Nora Elmadbouly, Alexandra R. Lucas, Jeanne Wilson-Rawls, Alan Rawls
Summary: Duchenne muscular dystrophy is a rare disease that affects males and current treatment options have serious side effects. A study suggests that a new immune-modulating protein called Pegylated Serp-1 can improve inflammation and fibrosis, potentially providing a new therapeutic approach for Duchenne muscular dystrophy.
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)
Review
Cell Biology
Elisa Domi, Malvina Hoxha, Emanuela Prendi, Bruno Zappacosta
Summary: Duchenne muscular dystrophy is a muscular disease with no cure, and SIRT1 has been identified as a potential therapeutic target for the condition. Activation of SIRT1 improves muscle function, while its inhibition leads to muscle fragility.
Review
Biochemistry & Molecular Biology
Krzysztof Zablocki, Dariusz C. Gorecki
Summary: Muscular dystrophies are inherited neuromuscular diseases that cause progressive disability and can reduce life expectancy. Loss of dystrophin or mutations in sarcoglycan-encoding genes lead to the loss of a-sarcoglycan ecto-ATPase activity, disrupting purinergic signaling and causing chronic inflammation in dystrophic muscles. Over-activation of P2X7 purinoceptors exacerbates pathology in dystrophic muscle cells. Blocking P2X7 receptors has shown promising results in mouse models and should be considered for the treatment of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Review
Clinical Neurology
Md Nur Ahad Shah, Toshifumi Yokota
Summary: Duchenne muscular dystrophy (DMD) is a devastating disease with life-limiting complications, especially in the respiratory and cardiac systems. Despite various therapies aimed at delaying disease progression, a cure for DMD is still elusive. Recent advancements include gene therapies, small molecule-based therapy, and cell therapy, but each has its own limitations and risks. This review summarizes approved and promising therapeutics for DMD, with a focus on cardiac manifestations.
THERAPEUTIC ADVANCES IN NEUROLOGICAL DISORDERS
(2023)
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
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
Clinical Neurology
Katharine C. Simon, Paola Malerba, Neal Nakra, Amy Harrison, Sara C. Mednick, Marni Nagel
Summary: This study measured slow oscillations in Duchenne and Becker muscular dystrophy male patients and found a significant decline in slow oscillation density with age. When patients were grouped by age, a decline in the rate and amplitude of slow oscillations was observed.
Article
Biochemistry & Molecular Biology
Yusuke Kawamura, Tetsuro Hida, Bisei Ohkawara, Masaki Matsushita, Takeshi Kobayashi, Shinya Ishizuka, Hideki Hiraiwa, Satoshi Tanaka, Mikito Tsushima, Hiroaki Nakashima, Kenyu Ito, Shiro Imagama, Mikako Ito, Akio Masuda, Naoki Ishiguro, Kinji Ohno
Summary: The anti-histamine drug meclozine promotes the proliferation and survival of human myogenic progenitor cells but inhibits myotube formation. In a mouse model of muscular dystrophy, meclozine improves muscle mass, exercise performance, and reduces ERK1/2 phosphorylation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Elena Gargaun, Sestina Falcone, Guilhem Sole, Julien Durigneux, Andoni Urtizberea, Jean Marie Cuisset, Sofia Benkhelifa-Ziyyat, Laura Julien, Anne Boland, Florian Sandron, Vincent Meyer, Jean Francois Deleuze, David Salgado, Jean-Pierre Desvignes, Christophe Beroud, Anatole Chessel, Alexia Blesius, Martin Krahn, Nicolas Levy, France Leturcq, France Pietri-Rouxel
Summary: This study found that long noncoding RNAs play important roles in Duchenne and Becker muscular dystrophy, particularly in regulating myocyte proliferation and differentiation with potential therapeutic implications. The research suggests that lncRNA44s2 may serve as an accelerator in muscle differentiation process and is associated with a favorable clinical phenotype.
Review
Clinical Neurology
Carlos Pascual-Morena, Vicente Martinez-Vizcaino, Alicia Saz-Lara, Jose Francisco Lopez-Gil, Jaime Fernandez-Bravo-Rodrigo, Ivan Cavero-Redondo
Summary: Dystrophin alterations in Becker and Duchenne muscular dystrophies are associated with an increased risk of epilepsy. This study aimed to estimate the prevalence of epilepsy in BMD and DMD populations and explore the association between dystrophin gene mutation site and epilepsy risk. The results showed a higher prevalence of epilepsy in BMD and DMD populations compared to the general population, but no significant association was found between mutation site and epilepsy risk.
JOURNAL OF NEUROLOGY
(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)
Article
Biochemistry & Molecular Biology
Norio Motohashi, Akiyoshi Uezumi, Atsushi Asakura, Madoka Ikemoto-Uezumi, Shuuichi Mori, Yuhei Mizunoe, Rumi Takashima, Yuko Miyagoe-Suzuki, Shin'ichi Takeda, Kazuhiro Shigemoto
CELL DEATH AND DIFFERENTIATION
(2019)
Article
Physiology
Angus Lindsay, Alexie A. Larson, Mayank Verma, James M. Ervasti, Dawn A. Lowe
JOURNAL OF APPLIED PHYSIOLOGY
(2019)
Article
Clinical Neurology
Mayank Verma, Yoko Asakura, Atsushi Asakura
Article
Multidisciplinary Sciences
Jong-Hee Kim, Ted G. Graber, Haiming Liu, Atsushi Asakura, LaDora V. Thompson
Review
Cell & Tissue Engineering
Andrew T. Crane, Rajagopal N. Aravalli, Atsushi Asakura, Andrew W. Grande, Venkatramana D. Krishna, Daniel F. Carlson, Maxim C-J Cheeran, Georgette Danczyk, James R. Dutton, Perry B. Hackett, Wei-Shou Hu, Ling Li, Wei-Cheng Lu, Zachary D. Miller, Timothy D. O'Brien, Angela Panoskaltsis-Mortari, Ann M. Parr, Clairice Pearce, Mercedes Ruiz-Estevez, Maple Shiao, Christopher J. Sipe, Nikolas G. Toman, Joseph Voth, Hui Xie, Clifford J. Steer, Walter C. Low
CELL TRANSPLANTATION
(2019)
Article
Genetics & Heredity
Mayank Verma, Yuko Shimizu-Motohashi, Yoko Asakura, James P. Ennen, Jennifer Bosco, Zhiwei Zhou, Guo-Hua Fong, Serene Josiah, Dennis Keefe, Atsushi Asakura
Article
Medicine, Research & Experimental
Darko Bosnakovski, Ahmed S. Shams, Ce Yuan, Meiricris T. da Silva, Elizabeth T. Ener, Cory W. Baumann, Angus J. Lindsay, Mayank Verma, Atsushi Asakura, Dawn A. Lowe, Michael Kyba
JOURNAL OF CLINICAL INVESTIGATION
(2020)
Article
Cell Biology
Nobuko Katoku-Kikyo, Ellen Paatela, Daniel L. Houtz, Britney Lee, Dane Munson, Xuerui Wang, Mohammed Hussein, Jasmeet Bhatia, Seunghyun Lim, Ce Yuan, Yoko Asakura, Atsushi Asakura, Nobuaki Kikyo
Summary: This study demonstrates that the circadian master regulators Per1 and Per2 play essential roles in regulating myoblast differentiation and muscle regeneration by controlling the activation of Igf2 and key genes in the differentiation process. The circadian epigenetic priming creates a preferred time window for initiating myoblast differentiation, with muscle regeneration being faster when initiated at night due to higher expression of Per1, Per2, and Igf2 compared to morning.
JOURNAL OF CELL BIOLOGY
(2021)
Article
Medicine, Research & Experimental
Jennifer Bosco, Zhiwei Zhou, Sofie Gabriels, Mayank Verma, Nan Liu, Brian K. Miller, Sheng Gu, Dianna M. Lundberg, Yan Huang, Eilish Brown, Serene Josiah, Muthuraman Meiyappan, Matthew J. Traylor, Nancy Chen, Atsushi Asakura, Natalie De Jonge, Christophe Blanchetot, Hans de Haard, Heather S. Duffy, Dennis Keefe
Summary: This study demonstrated that administration of specific antibodies could improve angiogenesis and promote muscle function recovery in patients with Duchenne muscular dystrophy.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Cell Biology
Huascar Pedro Ortuste Quiroga, Massimo Ganassi, Shingo Yokoyama, Kodai Nakamura, Tomohiro Yamashita, Daniel Raimbach, Arisa Hagiwara, Oscar Harrington, Jodie Breach-Teji, Atsushi Asakura, Yoshiro Suzuki, Makoto Tominaga, Peter S. Zammit, Katsumasa Goto
Summary: Piezo1 plays a crucial role in myogenic differentiation, with its activation enhancing myoblast fusion and its knockout suppressing fusion. These findings suggest that Piezo1 deregulation may impact muscle aging and degenerative diseases.
Article
Endocrinology & Metabolism
Shin Fujimaki, Tomohiro Matsumoto, Masashi Muramatsu, Hiroshi Nagahisa, Naoki Horii, Daiki Seko, Shinya Masuda, Xuerui Wang, Yoko Asakura, Yukie Takahashi, Yuta Miyamoto, Shingo Usuki, Kei-Ichiro Yasunaga, Yasutomi Kamei, Ryuichi Nishinakamura, Takashi Minami, Takaichi Fukuda, Atsushi Asakura, Yusuke Ono
Summary: Soluble Dll4 from endothelial cells triggers muscle atrophy via Notch2 signaling. Inhibition of the Dll4-Notch2 axis prevents muscle atrophy and promotes muscle hypertrophy.