Article
Clinical Neurology
Joel Iff, Charles Gerrits, Yi Zhong, Edward Tuttle, Erica Birk, Yeya Zheng, Xander Paul, Erik K. Henricson, Craig M. McDonald
Summary: This study evaluates the effect of eteplirsen treatment on pulmonary function in patients with DMD and finds that eteplirsen treatment significantly attenuates the decline in forced vital capacity and delays the need for ventilation and cough assist devices compared to standard of care.
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
Multidisciplinary Sciences
David P. Bishop, Mika T. Westerhausen, Florian Barthelemy, Thomas Lockwood, Nerida Cole, Elizabeth M. Gibbs, Rachelle H. Crosbie, Stanley F. Nelson, M. Carrie Miceli, Philip A. Doble, Jonathan Wanagat
Summary: This study introduces a novel immuno-mass spectrometry imaging method for quantifying and localizing dystrophin in muscle tissue. The method was validated in mice, human skeletal muscle sections, and DMD patients with different gene mutations, demonstrating its potential for pre-clinical and clinical research in DMD.
SCIENTIFIC REPORTS
(2021)
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
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
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
Yvan de Feraudy, Rabah Ben Yaou, Karim Wahbi, Caroline Stalens, Amalia Stantzou, Vincent Laugel, Isabelle Desguerre, Laurent Servais, France Leturcq, Helge Amthor
Summary: This study found that very low residual dystrophin protein quantity may lead to a shift in disease phenotype from DMD to BMD. Patients with dystrophin quantities <5% exhibited milder phenotypes for most clinical outcomes, including age at loss of ambulation.
ANNALS OF NEUROLOGY
(2021)
Review
Toxicology
Omar Sheikh, Toshifumi Yokota
Summary: Duchenne muscular dystrophy (DMD) is a severe genetic disease with no current cure. Eteplirsen, a promising exon-skipping therapy, faces challenges with low production of dystrophin and limited efficacy in the heart.
ARCHIVES OF TOXICOLOGY
(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.
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
Patricia Soblechero-Martin, Andrea Lopez-Martinez, Laura de la Puente-Ovejero, Ainara Vallejo-Illarramendi, Virginia Arechavala-Gomeza
Summary: Utrophin is a paralogue of dystrophin that can be overexpressed in the absence of dystrophin and may act as a surrogate to compensate for its deficiency. Various strategies to overexpress utrophin are being investigated, with many compounds showing promising results in preclinical studies by modulating utrophin expression and ameliorating the disease phenotype in animal models.
NEUROPATHOLOGY AND APPLIED NEUROBIOLOGY
(2021)
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)
Article
Medicine, General & Internal
Yuta Horikoshi, Norifumi Kuratani, Ken Tateno, Hiroshi Hoshijima, Tina Nakamura, Tsutomu Mieda, Katsushi Doi, Hiroshi Nagasaka
Summary: The use of remimazolam in pediatric patients with DMD undergoing general anesthesia was shown to be safe and effective, with careful monitoring of drug dosages and anesthesia depth being essential during the procedure.
Review
Biochemistry & Molecular Biology
Martina Sandona, Giorgia Cavioli, Alessandra Renzini, Alessia Cedola, Giuseppe Gigli, Dario Coletti, Timothy A. McKinsey, Viviana Moresi, Valentina Saccone
Summary: Histone deacetylases (HDACs) regulate the deacetylation of proteins, affecting cellular processes. Abnormal HDAC expression or activity is associated with various pathologies, making them potential therapeutic targets. For example, HDAC inhibitors have shown positive effects in preclinical and clinical studies for Duchenne Muscular Dystrophy (DMD). Understanding the cellular functions of HDACs in dystrophic muscles provides new insights for the development of effective therapeutic approaches.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(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.
