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
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
Biology
Tina Donandt, Stefan Hintze, Sabine Krause, Eckhard Wolf, Benedikt Schoser, Maggie C. Walter, Peter Meinke
Summary: Duchenne muscular dystrophy (DMD) is a common genetic disease in childhood, but there is no curative treatment yet. We established DMD pig models and an in vitro model for testing new therapies. This has significant implications for minimizing the use of live animals and supporting the 3R principle.
Article
Medicine, Research & Experimental
Flavien Bizot, Remko Goossens, Thomas Tensorer, Sergei Dmitriev, Luis Garcia, Annemieke Aartsma-Rus, Pietro Spitali, Aurelie Goyenvalle
Summary: This study found that histone deacetylase inhibitors can correct the imbalance of transcripts in patients with Duchenne muscular dystrophy, and the combined therapy with antisense oligonucleotides can significantly improve the restoration levels of dystrophin.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Immunology
Laura Yedigaryan, Ester Martinez-Sarra, Giorgia Giacomazzi, Nefele Giarratana, Bernard K. van der Veer, Alessio Rotini, Silvia Querceto, Hanne Grosemans, Alvaro Cortes-Calabuig, Sara Salucci, Michela Battistelli, Elisabetta Falcieri, Rik Gijsbers, Mattia Quattrocelli, Kian Peng Koh, Liesbeth De Waele, Gunnar M. Buyse, Rita Derua, Maurilio Sampaolesi
Summary: This study identifies an extracellular vesicle-derived miRNA signature that enhances the myogenic potential of myogenic stem cells, leading to improvements in muscle degeneration and muscle wasting related diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Multidisciplinary Sciences
Maria Sofia Falzarano, Martina Mietto, Fernanda Fortunato, Marianna Farne, Fernanda Martini, Pierpaolo Ala, Rita Selvatici, Francesco Muntoni, Alessandra Ferlini
Summary: This study investigated the transcription dynamics and spatial localization of the dystrophin (DMD) gene in DMD patients. The results showed significantly reduced DMD mRNA amount in the patients' cells and muscle biopsies, with a shift towards localization in the nuclei. This abnormal compartmentalization of mutant DMD mRNA contributes to the poor abundance and availability of dystrophin messenger in the cytoplasm.
SCIENTIFIC REPORTS
(2023)
Review
Oncology
Anna Rugowska, Alicja Starosta, Patryk Konieczny
Summary: Duchenne muscular dystrophy is a multisystem disorder that predominantly affects boys, caused by mutations in the DMD gene leading to changes in dystrophin expression profile. Loss of dystrophin results in muscle fiber disintegration and impaired regeneration, with associations to the loss of neuronal nitric oxide synthase.
CLINICAL EPIGENETICS
(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
Juan Shugert Aguayo, John M. Shelton, Wei Tan, Dinesh Rakheja, Chunyu Cai, Ahmed Shalaby, Jeon Lee, Susan T. Iannaccone, Lin Xu, Kenneth Chen, Dennis K. Burns, Yanbin Zheng
Summary: A new mouse model of muscular dystrophies (MD) driven by ectopic expression of PLAG1 was reported, which showed dystrophic features similar to human MD pathology. The study confirmed the repression of Dmd gene by ectopic PLAG1 expression and suggested the potential contribution of excess IGF2 in this model. This research provides new insights into the pathogenesis of MD and potential new treatment strategies.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
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
Biochemistry & Molecular Biology
Coralie Croissant, Romain Carmeille, Charlotte Brevart, Anthony Bouter
Summary: Muscular dystrophies are genetic disorders characterized by weakening and loss of skeletal muscle mass. ANXA proteins are important for membrane repair in cells, and dysregulation of ANXA expression may impact the clinical severity of muscular dystrophies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Alicja Starosta, Patryk Konieczny
Summary: DMD is a devastating X-linked disease characterized by progressive skeletal muscle wasting and heart dysfunction. Therapeutic strategies involving epigenetic modifications to modulate signal pathways have emerged as promising approaches. Taking a systemic view of DMD as a disease affecting muscle fibers and communication between different cell types may lead to holistic treatments that restore proper signal transmission and gene expression.
CELLULAR AND MOLECULAR LIFE SCIENCES
(2021)
Article
Immunology
Nicolas Dubuisson, Maria A. Davis-Lopez de Carrizosa, Romain Versele, Camille M. Selvais, Laurence Noel, P. Y. D. Van den Bergh, Sonia M. Brichard, Michel Abou-Samra
Summary: The study showed that specific inhibition of the NLRP3 inflammasome can significantly attenuate the dystrophic phenotype in DMD, leading to reduced inflammation and necrosis, as well as improved muscle maturation and function.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Cell Biology
Seung Yeon Jeong, Jun Hee Choi, Jooho Kim, Jin Seok Woo, Eun Hui Lee
Summary: TRIM32 is a conserved protein that plays multifunctional roles in maintaining skeletal muscle through its E3 ubiquitin ligase activity. Genetic variations in the TRIM32 gene are associated with skeletal muscular dystrophies in humans, particularly LGMD2H. These variations occur most frequently in the C-terminal NHL repeats of TRIM32.
Article
Psychology, Multidisciplinary
Rahul Tyagi, Harshita Arvind, Manoj Goyal, Akshay Anand, Manju Mohanty
Summary: The neuropsychological profile of Indian DMD subjects is not well understood and requires evaluation. Results show poor verbal and visual memory profiles in DMD patients, with working memory deficits being a crucial element of cognitive functioning. Working memory interventions may help improve neuropsychological profiles in DMD cases.
FRONTIERS IN PSYCHOLOGY
(2021)
Article
Physiology
Sabah N. Rezvani, Anne E. C. Nichols, Robert W. Grange, Linda A. Dahlgren, P. Gunnar Brolinson, Vincent M. Wang
Summary: Achilles tendinopathy is a challenging condition with limited effective therapies. This study introduced a novel mouse model of hindlimb muscle loading for targeted therapeutic exercise, showing promising results in improving biomechanical outcomes in a murine tendinopathy model. This model opens up possibilities for further research on how muscle loading can enhance healing of Achilles tendon injuries.
JOURNAL OF APPLIED PHYSIOLOGY
(2021)
Article
Endocrinology & Metabolism
Rebecca C. Knickmeyer, Crystal T. Nguyen, Jeffrey T. Young, Anne Haunton, Michael R. Kosorok, John H. Gilmore, Martin Styner, Debora A. Rothmond, Pamela L. Noble, Rhoshel Lenroot, Cynthia Shannon Weickert
Summary: The study found that prepubertal gonadectomy alters the developmental trajectory of prefrontal gray matter in male rhesus macaques, suggesting that the prefrontal cortex is more vulnerable to gonadectomy compared to other brain regions.
PSYCHONEUROENDOCRINOLOGY
(2021)
Article
Medicine, Research & Experimental
Shelby E. Hamm, Daniel D. Fathalikhani, Katherine E. Bukovec, Adele K. Addington, Haiyan Zhang, Justin B. Perry, Ryan P. McMillan, Michael W. Lawlor, Mariah J. Prom, Mark A. Vanden Avond, Suresh N. Kumar, Kirsten E. Coleman, J. B. Dupont, David L. Mack, David A. Brown, Carl A. Morris, J. Patrick Gonzalez, Robert W. Grange
Summary: The study showed that combining voluntary wheel running with microdystrophin gene therapy in young mdx mice improved whole-body performance, affected muscle function to varying degrees, mitigated energy deficits, but also revealed some detrimental effects of exercise.
MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT
(2021)
Article
Biochemistry & Molecular Biology
Danielle N. Rendina, Gabriele R. Lubach, Mark Lyte, Gregory J. Phillips, Ankush Gosain, Joseph F. Pierre, Roza M. Vlasova, Martin A. Styner, Christopher L. Coe
Summary: This study tracked the assembly of gut microbiota during the initial nursing period and transition to solid food in infant monkeys. The dynamic bacterial community structure reflected different maturational phases, influenced early by breast milk and later by solid foods. Higher abundance of certain microbial taxa during nursing was associated with slower growth trajectories and smaller brain volumes at one year of age.
Article
Multidisciplinary Sciences
Alexander L. Carlson, Kai Xia, M. Andrea Azcarate-Peril, Samuel P. Rosin, Jason P. Fine, Wancen Mu, Jared B. Zopp, Mary C. Kimmel, Martin A. Styner, Amanda L. Thompson, Cathi B. Propper, Rebecca C. Knickmeyer
Summary: Experimental manipulation of the gut microbiome in animal models impacts fear behaviors. This pilot study suggests associations between features of the human infant gut microbiome and non-social fear behaviors. Understanding the role of the gut microbiome in human fear behavior development requires further validation with a larger sample size.
NATURE COMMUNICATIONS
(2021)
Article
Nutrition & Dietetics
Brittney Knott, Matthew A. Kocher, Henry A. Paz, Shelby E. Hamm, William Fink, Jordan Mason, Robert W. Grange, Umesh D. Wankhade, Deborah J. Good
Summary: This study demonstrated that Snord116(m+/p-) mice and mice with a deletion of both Snord116 alleles showed weight and fat loss on a high-fat/CLA diet, indicating that the genotype did not interfere with CLA actions. There were no changes in food intake or metabolic rate, and only moderate differences in exercise performance. RNA-seq and microbiome analyses identified hypothalamic mRNAs and differentially populated gut bacteria, supporting future mechanistic analyses.
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
Genetics & Heredity
Kai Xia, Andrey A. Shabalin, Zhaoyu Yin, Wonil Chung, Patrick F. Sullivan, Fred A. Wright, Martin Styner, John H. Gilmore, Rebecca C. Santelli, Fei Zou
Summary: We developed an efficient alternative called TwinEQTL to the linear mixed-effects model for twin genome-wide association study data. TwinEQTL splits twin samples into two independent groups and combines the test results using a meta-analysis-like approach. Mathematical derivations and simulations show that TwinEQTL is valid and has comparable power to the gold-standard linear mixed-effects models.
Article
Public, Environmental & Occupational Health
Joshua R. Mann, Yanan Zhang, Suzanne McDermott, Yinding Wang, Bo Cai, Kristin M. Conway, Pangaja Paramsothy, Julie Royer, Swamy Venkatesh, James F. Howard, Emma Ciafaloni, MD STARnet
Summary: This study aimed to analyze whether there are racial/ethnic differences in the timing of diagnostic testing and treatments for males with Duchenne Muscular Dystrophy (DMD). The results showed significant delays for five of seven milestones in non-Hispanic Black individuals compared to non-Hispanic White individuals, while the findings for Hispanic individuals were less consistent. Efforts to address barriers to early evaluation and diagnosis for non-Hispanic Black children with DMD may promote more timely initiation of recommended disease monitoring and interventions.
Article
Clinical Neurology
Andreas Meisel, Djillali Annane, Tuan Vu, Renato Mantegazza, Masahisa Katsuno, Rasha Aguzzi, Glen Frick, Laura F. Gault, James Howard Jr
Summary: This study analyzed the interim results of an ongoing open-label extension study to evaluate the long-term treatment effects of ravulizumab in patients with anti-acetylcholine receptor antibody-positive generalized myasthenia gravis. The findings showed that ravulizumab demonstrated sustained efficacy and safety in improving the disease condition of patients.
JOURNAL OF NEUROLOGY
(2023)
Article
Clinical Neurology
Jeffrey T. Guptill, Michael Benatar, Volkan Granit, Ali A. Habib, James F. Howard, Carolina Barnett-Tapia, Richard J. Nowak, Ikjae Lee, Katherine Ruzhansky, Mazen M. Dimachkie, Gary R. Cutter, Henry J. Kaminski
Summary: The lack of standardization in outcome measures in myasthenia gravis clinical trials has led to confusion and variability in data. A group of experts summarized key outcome measures and made recommendations for improvements. Changes to outcome measure instructions and specific instruments were proposed, with a focus on the Quantitative MG score requiring the most attention. Training materials and revised documents will be made available to study teams.
Article
Genetics & Heredity
Sergey V. Prykhozhij, Lucia Caceres, Kevin Ban, Anna Cordeiro-Santanach, Kanneboyina Nagaraju, Eric P. Hoffman, Jason N. Berman
Summary: Limb-Girdle Muscular Dystrophy Type R1 (LGMDR1) is caused by CAPN3 mutations leading to progressive muscle weakness. The study generated zebrafish mutants to model LGMDR1 and found that capn3b is expressed in muscle. These mutants represent a novel model for studying muscle repair and remodeling, and as a preclinical tool for therapeutics and behavioral screening in LGMDR1.
Article
Clinical Neurology
Gianvito Masi, Minh C. C. Pham, Tabitha Karatz, Sangwook Oh, Aimee S. S. Payne, Richard J. J. Nowak, James F. F. Howard Jr, Jeffrey T. T. Guptill, Vern C. C. Juel, Kevin C. C. O'Connor
Summary: To compare the immunopathology of immune checkpoint inhibitor-induced myasthenia gravis (ICI-MG) and idiopathic MG, the researchers analyzed the AChR autoantibody pathogenic properties. They found that out of three ICI-MG patients with AChR autoantibodies, only one showed complement activation and modulation/blocking potency, similar to idiopathic MG. The other two patients did not exhibit AChR autoantibody-mediated effector functions, questioning the role of these antibodies in the pathology.
ANNALS OF CLINICAL AND TRANSLATIONAL NEUROLOGY
(2023)
Article
Clinical Neurology
Vera Bril, James F. Howard Jr, Chafic Karam, Jan L. De Bleecker, Hiroyuki Murai, Kimiaki Utsugisawa, Peter Ulrichts, Edward Brauer, Sihui Zhao, Renato Mantegazza, Tuan Vu, ADAPT Study Grp
Summary: Efgartigimod is beneficial in improving muscle function and strength across all muscle groups in patients with gMG by reducing IgG concentration and showing significant improvements in Myasthenia Gravis Activities of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores.
EUROPEAN JOURNAL OF NEUROLOGY
(2023)
Editorial Material
Medicine, Research & Experimental
Eric P. Hoffman
MOLECULAR THERAPY-NUCLEIC ACIDS
(2023)
Article
Rehabilitation
Gang Liu, Bradley Chi
Summary: This article provides a comprehensive review of the technological advances in the diagnosis and treatment of patients with a disorder of consciousness over the past 10 years. While these advances show promise, there is limited high-quality evidence supporting their widespread clinical adoption.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Amy Shapiro-Rosenbaum, Michelle P. Jaffe
Summary: Caregivers of persons with DoC experience high levels of perceived burden, which is associated with adverse physical, emotional, psychosocial, and financial outcomes and is directly tied to expressed needs for information and support. Providing individualized education and training at each phase of recovery can enhance effective communication between providers and caregivers, helping to increase caregiver proficiency in managing their loved one's care while also helping to mitigate the challenges associated with perceived burden. This may subsequently increase the rate of community discharge among persons with DoC, potentially translating to a reduction in the long-term costs of care for this population.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Jean E. Woo, Abana Azariah, Eboni A. Reed, Nicholas Gut
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Katherine O'Brien, Bei Zhang, Elizabeth Anderl, Sunil Kothari
Summary: Behavioral assessment is essential in the clinical evaluation of disorders of consciousness, and it should be supplemented by qualitative behavioral observations and individualized quantitative assessments. Therapy disciplines, staff, and family members all play important roles in this process.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Mary E. Russell, Cindy B. Ivanhoe, Eboni A. Reed
Summary: Acquired brain injury, especially severe brain injury, is a chronic medical condition that lacks research studies on postacute care and long-term outcomes. There is a need for standardized admission criteria, diagnostic tools, and prognostic protocols. Furthermore, healthcare systems should consider personalized factors and different perspectives on meaningful recovery and quality of life.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Brooke Murtaugh, Susan Fager, Tabatha Sorenson
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Amanda Appel, Eric Spier
Summary: This article discusses the importance of the emergence of consciousness in brain-injured patients and presents a framework for evaluating and tailoring treatment of sleep and pain. Although more research is needed, validated tools are currently available for assessing consciousness, pain, and sleep.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Kristen A. Harris, Yi Zhou, Stacey Jou, Brian D. Greenwald
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Ruth Tangonan, Christos Lazaridis
Summary: Acute disorders of consciousness refer to impairments in arousal and awareness that occur within 28 days of an initial injury, which can be caused by various insults. Thorough evaluations, including assessments of consciousness level, brainstem reflexes, and motor responses, are important. Laboratory tests, imaging, and electrophysiology testing are needed for the evaluation of acute disorders of consciousness. Prognostication in this phase should be done cautiously, with open and frequent communication with families, considering the significant multidimensional uncertainty.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Editorial Material
Rehabilitation
Sunil Kothari, Bei Zhang
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Michael H. Marino
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Linda B. Xu, Stephen Hampton, David Fischer
Summary: Neuroimaging in DoC has evolved to characterize complex brain networks and may have significant implications for understanding the natural history of DoC and optimizing long-term management.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
David B. Arciniegas, Lindsey J. Gurin, Bei Zhang
Summary: Understanding the neuroanatomy of wakefulness and awareness is crucial for clinicians dealing with disorders of consciousness. Wakefulness is supported by brainstem-forebrain-diencephalic systems, while awareness is a result of integrated activity within and between wakefulness systems and cortical areas. Disruptions in these neural systems can inform the clinical presentation and treatment options for disorders of consciousness.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Katherine Golden, Yelena G. Bodien, Joseph T. Giacino
Summary: This article discusses the classification associated with the four major disorders of consciousness (DoC): coma, vegetative state or unresponsive wakefulness syndrome, minimally conscious state, and post-traumatic confusional state. The history of each disorder are briefly reviewed and operational definitions and diagnostic criteria are provided. The article heavily relies on recently released practice guidelines and identifies knowledge gaps and discusses future directions to advance DoC research and practice.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)
Article
Rehabilitation
Beth S. Slomine, Stacy J. Suskauer
Summary: Research on children with disorders of consciousness (DoC) lags behind adult literature, and there is a lack of rigorous evaluation of assessment tools for this population. However, recent developments show promise in improving assessment for young children and those without overt command following. Early signs of consciousness are associated with better long-term outcomes. Although large clinical trials are lacking, programmatic data provide valuable information for standards of care and treatment options for children with DoC.
PHYSICAL MEDICINE AND REHABILITATION CLINICS OF NORTH AMERICA
(2024)