Article
Clinical Neurology
Daniele Sabbatini, Aurora Fusto, Sara Vianello, Matteo Villa, Joanna Janik, Grazia D'Angelo, Eleonora Diella, Francesca Magri, Giacomo P. Comi, Chiara Panicucci, Claudio Bruno, Adele D'Amico, Enrico Bertini, Guja Astrea, Roberta Battini, Luisa Politano, Riccardo Masson, Giovanni Baranello, Stefano C. Previtali, Sonia Messina, Gianluca Vita, Angela Berardinelli, Tiziana Mongini, Antonella Pini, Marika Pane, Eugenio Mercuri, Eric P. Hoffman, Lauren Morgenroth, Heather Gordish-Dressman, Tina Duong, Craig M. McDonald, Luca Bello, Elena Pegoraro
Summary: This study investigates the impact of modifiers on upper limb function in patients with DMD. The CD40 gene variant rs1883832 is found to be associated with upper limb functionality. These findings are important for the design and interpretation of clinical trials in DMD, especially for non-ambulatory patients.
JOURNAL OF NEUROLOGY
(2022)
Article
Cell Biology
Sholeh Bazrafshan, Hani Kushlaf, Mashhood Kakroo, John Quinlan, Richard C. Becker, Sakthivel Sadayappan
Summary: This study reviewed electronic medical records of 651 patients with neuromuscular disorders and identified novel genetic variants associated with cardiac abnormalities in eight patients with muscular dystrophy. Further investigation is needed to better understand the relationship between cardiac disease features and genetic mutations in patients with neuromuscular disorders.
Article
Genetics & Heredity
Ana Kosac, Jovan Pesovic, Lana Radenkovic, Milos Brkusanin, Nemanja Radovanovic, Marina Djurisic, Danijela Radivojevic, Jelena Mladenovic, Slavica Ostojic, Gordana Kovacevic, Ruzica Kravljanac, Dusanka Savic Pavicevic, Vedrana Milic Rasic
Summary: This study assessed the effect of the SPP1, CD40, and LTBP4 genes and DMD mutation location on loss of ambulation in patients with Duchenne muscular dystrophy. The results showed that the modifying effect of these genes was not replicated in Serbian patients, although the cohort was comparable to other European cohorts in terms of DMD mutation type distribution, SNP allele frequencies, and glucocorticoid corticosteroid therapy response. Cluster analysis may be able to identify patient subgroups carrying a combination of genetic variants that modify loss of ambulation.
Review
Chemistry, Medicinal
Carlos Pascual-Morena, Ivan Cavero-Redondo, Alicia Saz-Lara, Irene Sequi-Dominguez, Maribel Luceron-Lucas-Torres, Vicente Martinez-Vizcaino
Summary: This study aimed to assess the association of genetic variants involved in the TGF beta pathway with LoA and cardiac function in patients with DMD. The LTBP4 haplotype IAAM was found to have a protective effect on LoA, while no association was observed for the SPP1 rs28357094. The LTBP4 haplotype IAAM may be associated with a later LoA.
Article
Cell Biology
Brian J. Paleo, Kevin E. McElhanon, Hannah R. Bulgart, Kassidy K. Banford, Eric X. Beck, Kristina M. Sattler, Briana N. Goines, Shelby L. Ratcliff, Kelly E. Crowe, Noah Weisleder
Summary: TRIM72/MG53-mediated membrane repair can partially compensate for sarcolemmal fragility in DMD and the loss of membrane repair leads to increased pathology.
Article
Genetics & Heredity
Amihood Singer, Annemieke Aartsma-Rus, Julia Grinshpun-Cohen, Lena Sagi-Dain
Summary: The study summarizes the results of the first year of implementation of pan-ethnic screening testing for Duchenne muscular dystrophy (DMD) and discusses the challenges that follow. The study found clinically significant results in 82 cases, uncertain clinical significance in 80 cases, and false positive results in 373 cases initially identified as single-exon deletions. Interpreting population-based DMD carrier screening requires additional genetic testing methods and ethical considerations.
GENETICS IN MEDICINE
(2023)
Article
Neurosciences
Siyi Gan, Shulei Liu, Haiyan Yang, Liwen Wu
Summary: This study analyzed clinical data of 150 patients diagnosed with Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) in Hunan Children's Hospital, China. The study identified 150 small mutations, including 21 novel mutations. The analysis showed that positive family history, frameshift mutation, short duration of glucocorticoid (GC) treatment, and delayed GC treatment resulted in earlier loss of ambulation (LOA) for DMD patients. The findings provide important insights into the mutation spectrum of DMD/BMD and lay foundations for clinical trials.
FRONTIERS IN NEUROSCIENCE
(2022)
Editorial Material
Medicine, Research & Experimental
Jamie R. Johnston, Daniel F. Selgrade, Elizabeth M. McNally
Summary: Mutations in the LMNA gene are a common cause of adult-onset cardiomyopathy and heart failure, with a prenatal feature of impaired cardiomyocyte development and maturation identified in a Laminopathy model. Treatment of the LMNA H222P mouse model improved congenital cardiomyopathy and increased survival in utero, presenting a unique therapeutic strategy for cardiomyopathy.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Article
Medicine, Research & Experimental
Hiroaki Ohara, Motoyasu Hosokawa, Tomonari Awaya, Atsuko Hagiwara, Ryo Kurosawa, Yukiya Sako, Megumu Ogawa, Masashi Ogasawara, Satoru Noguchi, Yuichi Goto, Ryosuke Takahashi, Ichizo Nishino, Masatoshi Hagiwara
Summary: The FKTN c.647+2084G>T variant causes Fukuyama congenital muscular dystrophy (FCMD) by creating a pseudo-exon. Researchers discovered that the branchpoint, essential for splicing reactions, can be a potential therapeutic target. Through the design of branchpoint-targeted antisense oligonucleotides (BP-AONs), they successfully restored normal FKTN mRNA and protein production in FCMD patient myotubes. This suggests that branchpoints could be potential targets in exon-skipping therapeutic strategies for genetic disorders.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Physiology
Cory W. Baumann, Angus Lindsay, Sylvia R. Sidky, James M. Ervasti, Gordon L. Warren, Dawn A. Lowe
Summary: Our study found that maintenance of plasmalemmal excitability after eccentric contractions depends on intact and functional dystrophin glycoprotein complex (DGC) rather than solely dystrophin expression. Loss of torque after eccentric contractions was greater in dystrophic mouse lines compared to wild-type mice, showing the significant role of DGC in maintaining plasmalemmal excitability. Additionally, deficiency of the DGC protein beta-sarcoglycan was found to be equally disruptive to plasmalemmal excitability as dystrophin deficiency.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Engineering, Biomedical
Ainoa Tejedera-Villafranca, Marisol Montolio, Javier Ramon-Azcon, Juan M. Fernandez-Costa
Summary: This study developed a patient-derived functional 3D skeletal muscle model of DMD that reproduces the sarcolemmal damage found in the native DMD muscle. These bioengineered skeletal muscle tissues exhibit contractile functionality and mirror the pathological myotube breakdown in DMD. The study also evaluated the therapeutic effect of utrophin upregulator drug candidates on the functionality of the skeletal muscle tissues. The findings highlight the potential of bioengineered 3D skeletal muscle technology to advance DMD research and facilitate the development of novel therapies.
Review
Biochemistry & Molecular Biology
Vratko Himic, Kay E. Davies
Summary: Duchenne muscular dystrophy is a progressive muscle-wasting disorder caused by a lack of functional dystrophin, with limited effective treatments currently available. Novel genetic approaches show promise in treating DMD, with a focus on improving the limitations of gene editing and emphasizing the importance of early diagnosis and treatment.
EUROPEAN JOURNAL OF HUMAN GENETICS
(2021)
Article
Clinical Neurology
Marco Veneruso, Chiara Fiorillo, Paolo Broda, Serena Baratto, Monica Traverso, Alice Donati, Salvatore Savasta, Raffaele Falsaperla, Maria Margherita Mancardi, Marina Pedemonte, Chiara Panicucci, Gianluca Piatelli, Mattia Pacetti, Andrea Moscatelli, Luca Antonio Ramenghi, Lino Nobili, Carlo Minetti, Claudio Bruno
Summary: The role of muscle biopsy in diagnosing floppy infants is controversial as it is invasive and often non-specific, but still crucial in early infancy. Through a retrospective analysis, this study found that muscle biopsy results were consistent with genetic tests in 90% of cases, highlighting its importance in the diagnostic algorithm for hypotonia in infants.
FRONTIERS IN NEUROLOGY
(2021)
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
Pediatrics
Abdulaziz S. AlSaman, Fouad Al Ghamdi, Ahmed K. Bamaga, Nahla AlShaikh, Mohammed Al Muqbil, Osama Muthaffar, Fahad A. Bashiri, Baleegh Ali, Arzu Mulayim, Elena Heider, Abdullah A. Alshahrani, Mohammed A. Al Muhaizea
Summary: This study conducted an observational research on DMD patients in Saudi Arabia and found that the diagnosis age of DMD is relatively late, indicating a need for improved adherence to international DMD standard of care guidelines. Therefore, there is an urgent requirement for improved DMD education and awareness among healthcare professionals and the public in Saudi Arabia.
FRONTIERS IN PEDIATRICS
(2022)
Editorial Material
Medicine, Research & Experimental
Jamie R. Johnston, Daniel F. Selgrade, Elizabeth M. McNally
Summary: Mutations in the LMNA gene are a common cause of adult-onset cardiomyopathy and heart failure, with a prenatal feature of impaired cardiomyocyte development and maturation identified in a Laminopathy model. Treatment of the LMNA H222P mouse model improved congenital cardiomyopathy and increased survival in utero, presenting a unique therapeutic strategy for cardiomyopathy.
JOURNAL OF CLINICAL INVESTIGATION
(2021)
Review
Cardiac & Cardiovascular Systems
Arjun Sinha, Deepak K. Gupta, Clyde W. Yancy, Sanjiv J. Shah, Laura J. Rasmussen-Torvik, Elizabeth M. McNally, Philip Greenland, Donald M. Lloyd-Jones, Sadiya S. Khan
Summary: The article highlights the need for targeted prevention of heart failure, emphasizing the importance of quantifying individual patient risks in devising optimal prevention strategies. It discusses the development of HF risk prediction tools and the role of biomarkers in personalized risk estimation, as well as explores the application of genomics-enhanced approaches for HF prevention.
CIRCULATION-HEART FAILURE
(2021)
Article
Clinical Neurology
Alexis R. Demonbreun, Matthew P. Velez, Rana Saber, Daniel T. Ryan, Amelia Sancilio, Thomas W. McDade, Elizabeth M. McNally
Summary: Non-ambulatory neuromuscular disease patients show a strong immune response to two doses of mRNA COVID-19 vaccine, as indicated by elevated antibody levels similar to healthy vaccinated controls.
NEUROMUSCULAR DISORDERS
(2022)
Article
Cardiac & Cardiovascular Systems
Rabia S. Khan, Elfriede Pahl, Lisa Dellefave-Castillo, Karen Rychlik, Alexander Ing, Kai Lee Yap, Casey Brew, Jamie R. Johnston, Elizabeth M. McNally, Gregory Webster
Summary: Pediatric dilated cardiomyopathy (DCM) is a common cardiac disease, but the correlation between its phenotype and genotype is poorly understood. This study reviewed a large number of pediatric DCM cases and found that variations in sarcomeric genes are associated with age of diagnosis and cardiac outcomes.
JOURNAL OF THE AMERICAN HEART ASSOCIATION
(2022)
Article
Immunology
Mattia Quattrocelli, Michelle Wintzinger, Karen Miz, Manoj Panta, Ashok D. Prabakaran, Grant D. Barish, Navdeep S. Chandel, Elizabeth M. McNally
Summary: This study found that intermittent use of glucocorticoids can improve metabolic status, exercise tolerance, and energy expenditure in mice with diet-induced obesity. These effects are associated with the regulation of adiponectin, and are achieved through the modulation of glucocorticoid receptor and the CAMKK2-AMPK cascade in muscle metabolism.
JOURNAL OF EXPERIMENTAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Zhen Jiang, Selma Z. Elsarrag, Qiming Duan, Edward L. LaGory, Zhe Wang, Michael Alexanian, Sarah McMahon, Ingrid C. Rulifson, Sarah Winchester, Yi Wang, Christian Vaisse, Jonathan D. Brown, Mattia Quattrocelli, Charles Y. Lin, Saptarsi M. Haldar
Summary: This study reveals that hepatocyte KLF15 controls plasma corticosteroid transport and inflammatory responses through direct transcriptional activation of Serpina6. Moreover, KLF15 is predominantly enriched in the promoter regions of liver cells, regulating gene transcription activity through binding specific DNA sequences, with minimal associated gene repression.
Article
Endocrinology & Metabolism
Michelle Wintzinger, Manoj Panta, Karen Miz, Ashok D. Prabakaran, Hima Bindu Durumutla, Michelle Sargent, Clara Bien Peek, Joseph Bass, Jeffery D. Molkentin, Mattia Quattrocelli
Summary: This study investigates the regulatory effects of circadian-specific intermittent glucocorticoid treatment on cardiac metabolism and function, providing insights into the potential new therapeutic strategy for modulating heart metabolism.
MOLECULAR METABOLISM
(2022)
Article
Medicine, Research & Experimental
Alexis R. Demonbreun, Elena Bogdanovic, Lauren A. Vaught, Nina L. Reiser, Katherine S. Fallon, Ashlee M. Long, Claire C. Oosterbaan, Michele Hadhazy, Patrick G. T. Page, Prem Raj B. Joseph, Gabrielle Cowen, Alexander M. Telenson, Ammaarah Khatri, Katherine R. Sadleir, Robert Vassar, Elizabeth M. McNally
Summary: Annexin A6 plays a crucial role in membrane repair and can promote repair in multiple cell types. Recombinant annexin A6 may have potential in treating chronic disorders.
Editorial Material
Cardiac & Cardiovascular Systems
Elizabeth M. McNally, Karisma R. Chhabria, Dominic E. Fullenkamp
CIRCULATION-HEART FAILURE
(2023)
Article
Cardiac & Cardiovascular Systems
Lisa M. Wren, Jean-Marc Dekeyser, David Y. Barefield, Nicole A. Hawkins, Elizabeth M. Mcnally, Jennifer A. Kearney, J. Andrew Wasserstrom, Alfred L. George Jr
Summary: This study investigates the effects of different factors on the phenotype of calmodulinopathy and reveals the heterogeneity in arrhythmia susceptibility and cardiomyocyte Ca2+ dynamics among male and female mice with a recurrent pathogenic variant in Calm1 or Calm2.
CIRCULATION-ARRHYTHMIA AND ELECTROPHYSIOLOGY
(2023)
Article
Medicine, Research & Experimental
Isabella M. Salamone, Mattia Quattrocelli, David Y. Barefield, Patrick G. Page, Ibrahim Tahtah, Michele Hadhazy, Garima Tomar, Elizabeth M. McNally
Summary: Weekly glucocorticoid exposure produces different effects on skeletal muscle performance in male and female mice. Male muscles show enhanced response to weekly glucocorticoids, while female muscles exhibit significant upregulation of lipid metabolism genes.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Multidisciplinary Sciences
Mattia Quattrocelli, Michelle Wintzinger, Karen Miz, Daniel C. Levine, Clara Bien Peek, Joseph Bass, Elizabeth M. McNally
Summary: This study found that the timing of glucocorticoid intake can affect their effects on muscle bioenergetics. In mice, prednisone dosing during the light phase promoted NAD(+) levels and mitochondrial function, while dosing during the dark phase did not have the same effect. These results suggest that the circadian clock and muscle PGC1 alpha activity are important factors in glucocorticoid chronopharmacology for muscle bioenergetics.
Meeting Abstract
Cardiac & Cardiovascular Systems
Julie A. Fischer, Megan Puckelwartz, Matthew Wolf, Mattia Quattrocelli, Lorenzo Pesce, Rosemary Bauer, Samuel Kearns, Elizabeth M. McNally
CIRCULATION RESEARCH
(2021)
Meeting Abstract
Cardiac & Cardiovascular Systems
Mattia Quattrocelli, Michelle Wintzinger, Karen Miz
CIRCULATION RESEARCH
(2021)