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
Neurosciences
Susan Sienko, Cathleen E. Buckon, Anita Bagley, Loretta Staudt, Eileen Fowler, Kent Heberer, Mitell Sison-Williamson, Craig McDonald, Michael D. Sussman
Summary: In boys with DMD, walking energy cost increased over time as velocity decreased. Both NNcost and SMC-EC were identified as appropriate normalization schemes for the longitudinal assessment of energy cost in boys with DMD, showing similar sensitivity to age and differences in sensitivity to changes in height over time.
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
Eleonora S. D'Ambrosio, Jerry R. Mendell
Summary: Duchenne muscular dystrophy (DMD) is a childhood form of muscular dystrophy caused by mutations in the DMD gene, resulting in reduced or absent expression of dystrophin protein. Corticosteroids have been used to slow down disease progression, but genetically mediated therapies, such as exon skipping, gene replacement therapy, and gene editing with CRISPR technology, have emerged as the most promising treatment options for DMD.
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)
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
Pediatrics
Susan Jones, Ross Hanwell, Tharima Chowdhury, Jane Orgill, Kirandeep van den Eshof, Michael Farquhar, Desaline Joseph, Paul Gringras, Federica Trucco
Summary: The rapid implementation of home sleep studies during the COVID-19 lockdown in the UK was successful, but younger children and those with neurodevelopmental disorders, as well as patients with autism, had higher failure rates.
ARCHIVES OF DISEASE IN CHILDHOOD
(2022)
Article
Clinical Neurology
Kate Maresh, Andriani Papageorgiou, Deborah Ridout, Neil A. Harrison, William Mandy, David Skuse, Francesco Muntoni
Summary: Duchenne muscular dystrophy (DMD) patients, in addition to muscle loss, also experience intellectual disability and neurobehavioral co-morbidities. This study shows that boys with DMD exhibit increased startle responses to threat, similar to a DMD mouse model, and these responses normalize with dystrophin restoration.
Article
Clinical Neurology
Alberto A. Zambon, Vandana Ayyar Gupta, Deborah Ridout, Adnan Y. Manzur, Giovanni Baranello, Federica Trucco, Francesco Muntoni
Summary: This study aims to investigate the correlation between the North Star Ambulatory Assessment (NSAA) and timed rise from floor (TRF) with the age at loss of ambulation (LOA) in Duchenne muscular dystrophy (DMD). The findings show that higher functional abilities at peak are associated with older age at LOA in DMD. This information is important for counseling families and designing clinical trials.
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY
(2022)
Article
Respiratory System
Brigitte Fauroux, Francois Abel, Alessandro Amaddeo, Elisabetta Bignamini, Elaine Chan, Linda Corel, Renato Cutrera, Refika Ersu, Sophie Installe, Sonia Khirani, Uros Krivec, Omendra Narayan, Joanna MacLean, Valeria Perez De Sa, Marti Pons-Odena, Florian Stehling, Rosario Trindade Ferreira, Stijn Verhulst
Summary: Long-term noninvasive respiratory support in children is globally expanding, but there are still gaps in areas such as criteria for initiation and evaluation of long-term benefits. Therapeutic education and continuous support play a crucial role in improving patient adherence and quality of life.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Article
Clinical Neurology
Federica Trucco, Deborah Ridout, Joana Domingos, Kate Maresh, Mary Chesshyre, Pinki Munot, Anna Sarkozy, Stephanie Robb, Rosaline Quinlivan, Mollie Riley, Colin Wallis, Elaine Chan, Francois Abel, Silvana De Lucia, Jean-Yves Hogrel, Erik H. Niks, Imelda de Groot, Laurent Servais, Volker Straub, Valeria Ricotti, Adnan Manzur, Francesco Muntoni
Summary: The study investigated the respiratory progression in four DMD genotypes relevant in ongoing exon-skipping therapeutic strategies. Results showed that different genotypes have different effects on respiratory function, which is valuable for prognosis and evaluation of treatment options.
Correction
Clinical Neurology
Alejandro Lucia, Andrea Martinuzzi, Gisela Nogales-Gadea, Ros Quinlivan, Stacey Reason
NEUROMUSCULAR DISORDERS
(2022)
Article
Clinical Neurology
Alberto A. Zambon, Francois Abel, Barry Linnane, Declan O'Rourke, Rahul Phadke, Caroline A. Sewry, Anna Sarkozy, Adnan Manzur, Francesco Muntoni
Summary: Biallelic pathogenic variants in the TNNT1 gene cause severe congenital nemaline myopathy, characterized by motor delay, muscle weakness, chest wall deformities, respiratory muscle weakness, and early respiratory failure. This study reports on three unrelated patients with novel TNNT1 variants, demonstrating the challenges in managing respiratory support in these patients with the unique respiratory phenotype.
NEUROMUSCULAR DISORDERS
(2022)
Review
Rehabilitation
Clare M. Donnelly, Rosaline M. Quinlivan, Aaron Herron, Christopher D. Graham
Summary: Research findings suggest that parenting a child with DMD often involves experiencing a cycle of grief starting from diagnosis, as well as developing expertise in caregiving. In this process, parents may notice deviations from their and their child's expected life course and adjust their emotions and coping strategies to deal with uncertainty.
DISABILITY AND REHABILITATION
(2023)
Article
Multidisciplinary Sciences
Kate Maresh, Andriani Papageorgiou, Deborah Ridout, Neil Harrison, William Mandy, David E. Skuse, Francesco E. Muntoni
Summary: This study aimed to develop a novel task method to study startle responses in DMD patients and determine the most appropriate measurement index by optimizing data processing procedures. We successfully designed an effective discrimination fear-conditioning task and identified the optimal physiological outcome measure. Through this study, we will be able to gain a better understanding of startle responses in DMD patients.
Article
Clinical Neurology
Alberto A. Zambon, Federica Trucco, Aidan Laverty, Mollie Riley, Deborah Ridout, Adnan Y. Manzur, Francois Abel, Francesco Muntoni
Summary: This study aimed to investigate the prevalence and features of sleep disordered breathing (SDB) in pediatric patients with Duchenne muscular dystrophy (DMD) and explore the relationship between lung function and sleep abnormalities. The results showed a correlation between forced vital capacity (FVC) and the presence of nocturnal hypoventilation (NH). Additionally, some patients exhibited NH despite having FVC > 50%. These findings have important implications for the clinical management of SDB.
Article
Nutrition & Dietetics
Nicoline Lokken, Maja Risager Nielsen, Mads Godtfeldt Stemmerik, Charlotte Ellerton, Karoline Lolk Revsbech, Margaret Macrae, Anna Slipsager, Bjorg Krett, Gry Hatting Beha, Frida Emanuelsson, Gerrit van Hall, Rosaline Quinlivan, John Vissing
Summary: McArdle disease symptoms can be improved with a modified ketogenic diet, which increases fat oxidation and improves maximal exercise capacity.
CLINICAL NUTRITION
(2023)
Article
Clinical Neurology
Anna Sarkozy, Mario Sa, Deborah Ridout, Miguel Angel Fernandez-Garcia, Maria Grazia Distefano, Marion Main, Jennie Sheehan, Adnan Y. Manzur, Pinki Munot, Stephanie Robb, Elizabeth Wraige, Rosaline Quinlivan, Mariacristina Scoto, Giovanni Baranello, Vasantha Gowda, Rachael Mein, Rahul Phadke, Heinz Jungbluth, Francesco Muntoni
Summary: This study provides long-term data on the natural history of RYR1-related myopathies, with a focus on dominant and recessive forms of the disease. The results suggest that recessive patients have more severe clinical presentations, respiratory outcomes, and feeding outcomes compared to dominant patients. However, the longitudinal analysis indicates a slower progression of motor and respiratory function in recessive patients.
Meeting Abstract
Biochemistry & Molecular Biology
William Logan Macken, Caroline Mckittrick, Chiara Pizzamiglio, Enrico Bugiardini, Cathy Woodward, Robyn Labrum, Henry Houlden, Ros Quinlivan, Mike G. Hanna, Jana Vandrovcova, Robert D. S. Pitceathly
EUROPEAN JOURNAL OF HUMAN GENETICS
(2022)