Recent advancements in gene therapy have shown promise in addressing the molecular underpinnings of various myopathies, particularly Duchenne muscular dystrophy (DMD) and Myotonic Dystrophy type 1 (DM1). Moretti et al. demonstrated that somatic gene editing using sequence-specific nucleases can effectively restore the reading frame of the DMD gene in both pig models and patient-derived induced pluripotent stem cells, leading to the expression of a functional dystrophin protein (ref: Moretti doi.org/10.1038/s41591-019-0738-2/). In a complementary approach, Stepniak-Konieczna et al. explored antisense oligonucleotide (AON)-mediated splice-switching and degradation of mutated DMPK pre-mRNA as a therapeutic strategy for DM1, highlighting the potential of targeting RNA processing abnormalities caused by CUG-expanded transcripts (ref: Stepniak-Konieczna doi.org/10.1093/nar/). Furthermore, Himelman et al. identified a critical role for connexin-43 remodeling in DMD cardiomyopathy, linking hypophosphorylation of this gap junction protein to cardiac dysfunction in DMD models (ref: Himelman doi.org/10.1172/JCI128190/). Bianchi et al. further elucidated the molecular mechanisms of muscular dystrophies by investigating the role of polycomb group proteins in lamin A/C-dependent muscular dystrophy, revealing how their deregulation can lead to muscle stem cell dysfunction (ref: Bianchi doi.org/10.1172/JCI128161/). Lastly, Puy et al. assessed the impact of CTG expansions in the DMPK gene on semen quality, providing insights into reproductive implications associated with myopathies (ref: Puy doi.org/10.1210/clinem/).

The landscape of clinical and therapeutic interventions for muscular dystrophies is evolving, with innovative models and trials paving the way for precision medicine. Osaki et al. introduced a 3D neuromuscular model for drug screening, which integrates motor neurons and skeletal muscle cells derived from patient-specific induced pluripotent stem cells, thereby facilitating the study of neuromuscular diseases including muscular dystrophies (ref: Osaki doi.org/10.1038/s41596-019-0248-1/). In a clinical context, Naarding et al. demonstrated that quantitative MRI of the vastus lateralis fat fraction can serve as a predictive biomarker for loss of ambulation in DMD, emphasizing the utility of imaging techniques in monitoring disease progression (ref: Naarding doi.org/10.1212/WNL.0000000000008939/). Komaki et al. conducted a phase 2 trial of TAS-205 in DMD patients, revealing modest changes in the 6-minute walk distance, which underscores the challenges in developing effective therapies for this progressive condition (ref: Komaki doi.org/10.1002/acn3.50978/). Additionally, Xiong et al. identified novel candidate alleles associated with Emery-Dreifuss muscular dystrophy, enhancing our understanding of the genetic heterogeneity and clinical variability in this disorder (ref: Xiong doi.org/10.1016/j.ebiom.2019.102620/). These studies collectively highlight the importance of integrating novel therapeutic strategies with robust clinical assessments to improve outcomes for patients with muscular dystrophies.

Understanding the pathophysiology of myopathies is crucial for developing effective biomarkers and therapeutic strategies. Vagnozzi et al. investigated the transcriptional programs of phrenic motor neurons, revealing that Hox5 transcription factors play a significant role in shaping respiratory motor output, which is critical for diaphragm function (ref: Vagnozzi doi.org/10.7554/eLife.52859/). Capitanio et al. conducted comparative proteomic analyses between DMD and Becker muscular dystrophy (BMD) muscles, finding that while both conditions exhibit muscle wasting, BMD retains some metabolic functions that may contribute to preserved muscle function compared to DMD (ref: Capitanio doi.org/10.1002/jcsm.12527/). Karino et al. identified myofascia-dominant involvement as a risk factor for rapidly progressive interstitial lung disease in dermatomyositis, suggesting that whole-body MRI can be a valuable tool in assessing disease severity (ref: Karino doi.org/10.1093/rheumatology/). Todd et al. explored the efficacy of N-acetylcysteine in a randomized controlled trial, highlighting its potential to reduce oxidative stress in myopathy patients, although the results necessitate further investigation (ref: Todd doi.org/10.1212/WNL.0000000000008872/). These findings underscore the complexity of myopathy pathophysiology and the need for multifaceted approaches to biomarker development.

Rehabilitation strategies for myopathy patients are increasingly focusing on optimizing muscle function through innovative approaches. Lewis et al. emphasized the importance of codon optimization for the efficient allotopic expression of mitochondrial DNA genes, which could enhance gene therapy strategies for mitochondrial myopathies (ref: Lewis doi.org/10.1016/j.redox.2020.101429/). Watson et al. reported that patients with non-dialysis dependent chronic kidney disease (CKD) exhibit reduced skeletal muscle mitochondrial mass, and while exercise training increased PGC-1α expression, it did not restore mitochondrial biogenesis, indicating the need for tailored rehabilitation programs (ref: Watson doi.org/10.1096/fj.201901936RR/). Parenté et al. studied the effects of GASP-2 overexpression in mice, revealing a hypermuscular phenotype that contrasts with GASP-1 transgenics, suggesting potential pathways for muscle growth modulation (ref: Parenté doi.org/10.1096/fj.201901220R/). Lassche et al. investigated single muscle fiber contractile performance in facioscapulohumeral muscular dystrophy (FSHD), finding preserved specific force, which may inform rehabilitation strategies aimed at maintaining muscle function (ref: Lassche doi.org/10.1212/WNL.0000000000008977/). Collectively, these studies highlight the importance of understanding muscle biology and the potential for targeted rehabilitation interventions.

Genetic research continues to unveil critical insights into the progression of myopathies, particularly in understanding the implications of genetic mutations. Meyers et al. developed a DMD carrier model that exhibited mosaic dystrophin expression in the heart, revealing complex vulnerabilities to myocardial injury, which may inform future therapeutic strategies (ref: Meyers doi.org/10.1093/hmg/). Golman et al. proposed a novel classification system for partial patellar tendon tears, which could enhance diagnostic accuracy and treatment decisions, reflecting the need for precise genetic and imaging assessments in myopathy management (ref: Golman doi.org/10.1177/0363546519894333/). The study by Ajime et al. on the effects of smoking cessation on skeletal muscle atrophy and mitochondrial dysfunction further emphasizes the interplay between lifestyle factors and genetic predispositions in muscle health (ref: Ajime doi.org/10.1093/ntr/). Moretti et al. reiterated the significance of somatic gene editing in ameliorating muscle failure in DMD, reinforcing the potential of genetic interventions in altering disease trajectories (ref: Moretti doi.org/10.1038/s41591-019-0738-2/). These findings collectively underscore the intricate relationship between genetic factors and disease progression in myopathies, highlighting the potential for targeted interventions.

The role of inflammation and immune responses in myopathies is gaining recognition, with studies elucidating the underlying mechanisms. Vernerová et al. investigated the activin A-myostatin-follistatin system in inflammatory myopathies, finding altered levels of myostatin and follistatin in patients, which may contribute to muscle wasting (ref: Vernerová doi.org/10.1093/rheumatology/). Mandelli et al. explored the immune contexture of basal-type urothelial bladder cancer, noting the significance of tumor-infiltrating neutrophils, which may have parallels in understanding immune responses in myopathies (ref: Mandelli doi.org/10.3390/cells9020291/). Pierce et al. examined the impact of abuse history on pain medication side effects, suggesting that centralized pain mechanisms may be influenced by inflammatory processes, a consideration relevant to myopathy patients experiencing chronic pain (ref: Pierce doi.org/10.1136/rapm-2019-101130/). Furthermore, Watson et al. highlighted the persistent reductions in mitochondrial mass in CKD patients despite exercise training, indicating that inflammation may play a role in muscle dysfunction (ref: Watson doi.org/10.1096/fj.201901936RR/). These studies collectively emphasize the need for a deeper understanding of inflammatory pathways in myopathies to develop effective therapeutic strategies.

Exercise and lifestyle interventions are critical components of managing myopathies, with emerging evidence supporting their efficacy. Ajime et al. demonstrated that smoking cessation can reverse cigarette smoke-induced skeletal muscle atrophy and mitochondrial dysfunction in mice, highlighting the immediate benefits of lifestyle changes on muscle health (ref: Ajime doi.org/10.1093/ntr/). Stepniak-Konieczna et al. explored the potential of AON-induced splice-switching as a therapeutic approach for Myotonic Dystrophy type 1, indicating that lifestyle factors may interact with genetic therapies to improve outcomes (ref: Stepniak-Konieczna doi.org/10.1093/nar/). Lewis et al. emphasized the importance of codon optimization for effective gene therapy, suggesting that lifestyle interventions could be complemented by genetic strategies to enhance muscle function (ref: Lewis doi.org/10.1016/j.redox.2020.101429/). Watson et al. reported that exercise training did not restore mitochondrial mass in CKD patients, indicating that tailored exercise regimens are necessary to address specific deficits in muscle function (ref: Watson doi.org/10.1096/fj.201901936RR/). Yamaguchi et al. investigated urinary titin fragments as biomarkers for exercise-induced muscle damage, suggesting that monitoring these markers could inform exercise interventions (ref: Yamaguchi doi.org/10.1016/j.jsams.2019.12.023/). Together, these findings underscore the importance of integrating exercise and lifestyle modifications into comprehensive myopathy management strategies.

Diagnostic imaging plays a pivotal role in assessing myopathies, providing insights into disease progression and treatment efficacy. Naarding et al. demonstrated that quantitative MRI of the vastus lateralis fat fraction can predict loss of ambulation in Duchenne muscular dystrophy, establishing a valuable imaging biomarker for clinical assessments (ref: Naarding doi.org/10.1212/WNL.0000000000008939/). This study highlights the potential of imaging techniques to monitor disease progression and inform therapeutic decisions. The integration of advanced imaging modalities with clinical evaluations is essential for optimizing patient management. As the field evolves, the development of standardized imaging protocols and biomarkers will enhance the ability to track disease progression and response to interventions, ultimately improving outcomes for patients with myopathies.