Myopathy and muscle disorders encompass a range of genetic and acquired conditions that lead to muscle weakness and dysfunction. A significant focus has been on Facioscapulohumeral muscular dystrophy (FSHD), which is linked to deletions in the D4Z4 macrosatellite at chromosome 4q35. Research has shown that the long noncoding RNA FRG2A plays a crucial role in muscle-specific protein synthesis, with its expression levels varying among patients (ref: Salsi doi.org/10.1093/nar/). Additionally, iron accumulation in muscle tissues has been implicated in FSHD pathogenesis, and iron supplementation has been found to alleviate muscle pathologies in mouse models (ref: Nakamura doi.org/10.1172/JCI181881/). Another area of interest is centronuclear myopathy (CNM), where exon skipping therapies targeting the DNM2 gene have shown promise, although recent clinical trials revealed some non-muscle toxicity (ref: Moschovaki-Filippidou doi.org/10.1093/brain/). Furthermore, mitochondrial cardiomyopathies, which often present with skeletal myopathy, highlight the complex interplay between genetic mutations and muscle function (ref: Maack doi.org/10.1093/eurheartj/). Overall, these studies underscore the need for targeted therapies and a deeper understanding of the molecular mechanisms underlying these disorders.

Chronic fatigue syndromes, particularly Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) and Long COVID, present significant challenges in diagnosis and management due to their multifactorial nature. Recent studies have identified oxidative stress as a common characteristic of both conditions, with elevated levels observed in peripheral blood lymphocytes of patients (ref: Shankar doi.org/10.1073/pnas.2426564122/). Additionally, a comprehensive treatment survey involving 3,925 patients revealed insights into patient-reported outcomes, highlighting the urgent need for effective management strategies (ref: Eckey doi.org/10.1073/pnas.2426874122/). The use of AI-driven multi-omics modeling has also emerged as a promising approach to identify disease-specific biomarkers and classify ME/CFS, indicating a potential shift towards personalized medicine (ref: Xiong doi.org/10.1038/s41591-025-03788-3/). Furthermore, the risk of developing new-onset CFS/ME post-SARS-CoV-2 infection has been quantified, revealing higher susceptibility among females and those with pre-existing conditions (ref: Hadidchi doi.org/10.1186/s12967-025-06625-w/). These findings emphasize the interconnectedness of metabolic dysregulation and immune response in chronic fatigue syndromes.

The exploration of genetic and molecular mechanisms in myopathies has revealed critical insights into the pathophysiology of various muscle disorders. For instance, the study of eukaryotic linear motifs governing androgen receptor function has provided a deeper understanding of gene expression regulation across species, highlighting evolutionary adaptations (ref: Falconieri doi.org/10.1093/nar/). Mitochondrial dysfunction remains a central theme, particularly in mitochondrial cardiomyopathies, where genetic mutations disrupt energy production and lead to multisystemic symptoms (ref: Maack doi.org/10.1093/eurheartj/). Additionally, the late-stage transcriptomic analysis in Duchenne muscular dystrophy (DMD) has uncovered a BMP4-induced molecular signature, suggesting potential therapeutic targets for late-stage interventions (ref: Sothers doi.org/10.1002/jcsm.70005/). The identification of shared metabolic dysregulations in conditions like ME/CFS and Long COVID further illustrates the complexity of muscle disorders and the need for integrated approaches to treatment (ref: Li doi.org/10.3390/ijms26136082/).

Therapeutic strategies for muscle disorders are rapidly evolving, with a focus on innovative approaches such as gene therapy and regenerative medicine. One promising avenue involves the use of exon skipping peptide-conjugated morpholinos to target DNM2 in centronuclear myopathy, although recent trials have indicated some limitations due to non-muscle toxicity (ref: Moschovaki-Filippidou doi.org/10.1093/brain/). Additionally, the development of a clinical-grade myogenic progenitor product derived from induced pluripotent stem cells (iPSCs) has shown potential for treating muscular dystrophies, demonstrating long-term engraftment and efficacy in preclinical models (ref: Azzag doi.org/10.1016/j.ymthe.2025.07.007/). The use of Opantimirs, a class of antagonizing microRNAs, has also been shown to enhance mitochondrial function and improve muscle strength in models of disuse myopathy (ref: Djalalvandi doi.org/10.1016/j.xcrm.2025.102248/). These advancements highlight the importance of personalized and targeted therapies in addressing the complexities of muscle disorders.

The role of inflammation and immune response in myopathies has gained attention, particularly in the context of chronic conditions like ME/CFS and Long COVID. Elevated oxidative stress has been identified as a shared characteristic of these syndromes, indicating a potential link between immune dysregulation and muscle pathology (ref: Shankar doi.org/10.1073/pnas.2426564122/). Furthermore, the investigation of monocyte subsets and fibrosis-related genes in muscular dystrophy patients undergoing prednisone therapy has revealed insights into the inflammatory landscape of dystrophic muscle (ref: Chikhaoui doi.org/10.3390/ijms26135992/). The impact of rapid access strategies on the diagnosis and treatment of polymyalgia rheumatica also underscores the importance of timely intervention in inflammatory muscle disorders (ref: Nielsen doi.org/10.1016/j.semarthrit.2025.152793/). These findings emphasize the need for a comprehensive understanding of the immune mechanisms involved in muscle disorders to develop effective therapeutic strategies.

Metabolic dysregulation plays a crucial role in the pathophysiology of muscle disorders, particularly in conditions like ME/CFS and Long COVID. Studies have demonstrated overlapping metabolic symptoms in these syndromes, suggesting shared underlying dysfunctions that warrant further exploration (ref: Li doi.org/10.3390/ijms26136082/). The investigation of DNA methylation patterns in peripheral blood from patients with ME/CFS and Long COVID has provided insights into the molecular alterations associated with these conditions, highlighting potential biomarkers for diagnosis and treatment (ref: Peppercorn doi.org/10.3390/ijms26146631/). Additionally, oxidative stress has been identified as a common feature, reinforcing the link between metabolic disturbances and immune response in these syndromes (ref: Shankar doi.org/10.1073/pnas.2426564122/). Overall, these findings underscore the importance of addressing metabolic dysregulation in the management of muscle disorders.

Clinical and patient-reported outcomes are essential for understanding the impact of muscle disorders on patients' lives and guiding treatment strategies. A recent survey involving 3,925 patients with ME/CFS and Long COVID revealed valuable insights into treatment experiences and outcomes, highlighting the need for effective management approaches in the absence of FDA-approved therapies (ref: Eckey doi.org/10.1073/pnas.2426874122/). The identification of elevated oxidative stress in these patients further emphasizes the importance of monitoring clinical outcomes related to metabolic health (ref: Shankar doi.org/10.1073/pnas.2426564122/). Additionally, the risk factors for developing new-onset CFS/ME post-COVID-19 infection, particularly among vulnerable populations, underscore the need for ongoing surveillance and tailored interventions (ref: Hadidchi doi.org/10.1186/s12967-025-06625-w/). These findings highlight the significance of integrating patient-reported outcomes into clinical practice to enhance care for individuals with muscle disorders.

Neurodegeneration and muscle weakness are interconnected phenomena observed in various myopathies, with recent studies shedding light on underlying mechanisms. The role of mitochondrial dysfunction in muscle disorders has been emphasized, particularly in the context of aging and neurodegenerative diseases. For instance, Opantimirs have been shown to enhance mitochondrial function and muscle strength in models of disuse myopathy, indicating potential therapeutic applications (ref: Djalalvandi doi.org/10.1016/j.xcrm.2025.102248/). Additionally, the exploration of epilepsy in the context of L-arginine:glycine amidinotransferase deficiency has expanded the phenotype of this condition, revealing complex interactions between metabolic and neurological factors (ref: Ferretti doi.org/10.1111/epi.18565/). Furthermore, aberrant lysosomal dynamics in X-linked myotubular myopathy have been linked to disrupted myogenesis, highlighting the need for a comprehensive understanding of neurodegenerative processes in muscle disorders (ref: Kora doi.org/10.1093/brain/). These insights underscore the importance of addressing both neurodegenerative and muscular aspects in the management of related conditions.