The exploration of genetic and molecular mechanisms underlying myopathies has revealed significant insights into various conditions, particularly amyotrophic lateral sclerosis (ALS) and facioscapulohumeral muscular dystrophy (FSHD). The identification of pathogenic variants in the SOD1 gene has been pivotal in understanding ALS, leading to the development of transgenic rodent models that facilitate the study of SOD1 ALS biology. These models have illuminated the toxic gain-of-function mutations driving the disease, prompting therapeutic strategies aimed at reducing SOD1 protein levels, although the phenotypic heterogeneity of SOD1 ALS complicates treatment approaches (ref: Benatar doi.org/10.1016/S1474-4422(24)00479-4/). In FSHD, a study employing mediation analyses demonstrated that age at onset (AAO) significantly influences disease severity, accounting for substantial portions of the effects of genetic factors such as D4Z4 repeat units and CpG6 methylation levels on clinical outcomes (ref: Zheng doi.org/10.1093/brain/). Furthermore, a meta-analysis of idiopathic inflammatory myopathies (IIMs) identified novel risk loci and susceptibility genes, emphasizing the strong genetic component that influences disease progression and clinical manifestations (ref: Zhu doi.org/10.1002/art.43088/). Additionally, research on muscle stem cell dysfunction in mdx mice has highlighted intrinsic cellular impairments contributing to impaired muscle regeneration, revealing architectural and functional changes post-injury (ref: Esper doi.org/10.1002/jcsm.13682/). The investigation into Stathmin-2 (STMN2) as a therapeutic target for spinal muscular atrophy (SMA) has also emerged, indicating the need for strategies beyond SMN replacement therapies (ref: Pagliari doi.org/10.1007/s00018-024-05550-3/). Lastly, altered metabolic profiles in dermatomyositis associated with different myositis-specific autoantibodies have been linked to disease activity, suggesting potential avenues for early diagnosis and therapeutic targeting (ref: Wang doi.org/10.3389/fimmu.2024.1429010/).

Clinical trials focusing on therapeutic approaches for myopathies have made significant strides, particularly in the context of rare diseases and spinal muscular atrophy (SMA). A phase 1a/1b randomized study evaluated KL1333, a novel oral molecule, for its safety and tolerability in adults with mitochondrial disease, addressing the unique challenges of clinical trial design for rare disorders (ref: Pizzamiglio doi.org/10.1093/brain/). In the realm of SMA, a nationwide study reported on the impact of disease-modifying treatments (DMTs) on survival and functional outcomes in children with type I SMA born since the introduction of these therapies in Italy. The findings highlighted a significant shift in the natural history of the disease, showcasing improved survival rates and functional abilities (ref: Pera doi.org/10.1016/j.eclinm.2024.102967/). Additionally, the use of ultrasound to assess dactylitis has been shown to correlate with the early diagnosis of psoriatic arthritis, indicating the potential for imaging techniques to enhance diagnostic accuracy in myopathy-related conditions (ref: Olivas-Vergara doi.org/10.1016/j.semarthrit.2024.152612/). Furthermore, a study investigating nailfold videocapillaroscopy (NVC) findings in idiopathic inflammatory myopathies revealed correlations with lung outcomes, emphasizing the importance of integrating imaging biomarkers in clinical assessments (ref: Sieiro Santos doi.org/10.1093/rheumatology/). These studies collectively underscore the evolving landscape of clinical trials and therapeutic strategies aimed at improving outcomes for patients with myopathies.

Research into the pathophysiology and biomarkers of myopathies has unveiled critical insights into disease mechanisms and potential therapeutic targets. In myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), a multiomic analysis revealed transcriptional reprogramming that primes CD8+ T cells toward exhaustion, highlighting immune dysregulation as a significant contributor to the disease (ref: Iu doi.org/10.1073/pnas.2415119121/). Similarly, longitudinal imaging studies in the mouse model of Charlevoix-Saguenay ataxia have identified retinal nerve fiber layer thickening as a distinctive biomarker, correlating with clinical progression and providing a model for future biomarker studies in human patients (ref: Gigliucci doi.org/10.1002/ana.27146/). In spinal muscular atrophy (SMA), the upregulation of inflammatory cytokines by astrocytes has been implicated in motor neuron loss, suggesting that targeting IL-1ra and CCL5 may offer new therapeutic avenues (ref: Allison doi.org/10.1016/j.ymthe.2024.12.016/). Additionally, a randomized controlled trial on fibromyalgia demonstrated that a web-based intervention could enhance emotional well-being and reduce pain, indicating the potential for psychological approaches in managing chronic pain conditions (ref: Ong doi.org/10.2196/54678/). Lastly, the regulation of glucose transporter 4 (GLUT4) in muscle regeneration post-injury has been investigated, revealing that GLUT4 does not significantly impair muscle regeneration, thus prompting further exploration of metabolic pathways in muscle repair (ref: Sermersheim doi.org/10.1186/s13395-024-00366-y/).

Neuroimmune interactions play a pivotal role in the pathophysiology of myopathies, particularly in conditions such as Long COVID and fibromyalgia. A study examining the immune and neuronal dysregulation in Long COVID patients revealed upregulation of olfactory receptors and neuronal-associated genes, suggesting a complex interplay between immune responses and neurological symptoms similar to those observed in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) (ref: Shahbaz doi.org/10.1016/j.bbi.2024.11.032/). Furthermore, the correlation of nailfold videocapillaroscopy findings with lung outcomes in idiopathic inflammatory myopathies underscores the significance of vascular and immune interactions in disease progression (ref: Sieiro Santos doi.org/10.1093/rheumatology/). In fibromyalgia, research has shown that metformin can modulate neurotransmitter levels and reduce pro-inflammatory cytokines, indicating a potential neuroimmune mechanism underlying the condition (ref: AboTaleb doi.org/10.3390/cells13231986/). Additionally, the investigation into TIA1-dependent stress granules has provided insights into the molecular grammar of neuroimmune interactions, particularly in the context of Welander distal myopathy under oxidative stress (ref: Alcalde-Rey doi.org/10.3390/cells13231961/). Collectively, these studies highlight the intricate relationships between the nervous system and immune responses in myopathies, paving the way for novel therapeutic strategies.

Muscle regeneration and repair mechanisms are critical areas of research in understanding myopathies, particularly in models such as the mdx mouse, which is widely used to study Duchenne muscular dystrophy (DMD). A study investigating the role of intrinsic muscle stem cell dysfunction in mdx mice revealed significant architectural and functional changes following acute injury, including impaired recovery of maximum tetanic force and reduced myocyte numbers (ref: Esper doi.org/10.1002/jcsm.13682/). Furthermore, the deletion of Wnt7a in muscle has been shown to hinder regeneration in both wild-type and mdx mice, indicating the importance of Wnt signaling in muscle repair processes (ref: Gurriaran-Rodriguez doi.org/10.1186/s13395-024-00367-x/). Comparative lipidomic and metabolomic profiling of mdx and severe mdx-apolipoprotein E-null mice has also highlighted metabolic dysregulation as a contributing factor to myofiber damage, suggesting that metabolic interventions may enhance muscle regeneration (ref: Khattri doi.org/10.1186/s13395-024-00368-w/). Additionally, a systematic review on exercise therapy for chronic fatigue syndrome has raised questions about the efficacy and safety of such interventions, emphasizing the need for further research to clarify the benefits and risks associated with exercise in muscle repair contexts (ref: Larun doi.org/10.1002/14651858.CD003200.pub9/). Together, these findings underscore the complexity of muscle regeneration mechanisms and the potential for targeted therapies to improve outcomes in myopathy patients.

The impact of pain and quality of life in patients with myopathies is a critical area of investigation, particularly in conditions such as fibromyalgia and chronic fatigue syndrome. A study profiling microRNA and transfer RNA fragment levels in patients with fibromyalgia revealed distinct patterns associated with disease severity, suggesting that these small noncoding RNAs may serve as potential biomarkers for fibromyalgia (ref: Erbacher doi.org/10.1097/j.pain.0000000000003499/). Additionally, the effectiveness of transitioning from a very low-calorie ketogenic diet (VLCKD) to a low-glycemic and insulinemic (LOGI) regimen was assessed in fibromyalgia patients, indicating that while some clinical improvements were noted, symptoms persisted, highlighting the need for sustainable dietary strategies in managing fibromyalgia (ref: Castaldo doi.org/10.3390/nu16234161/). A systematic review examining the relationship between serum vitamin D levels and chronic musculoskeletal pain found inconclusive evidence regarding direct associations, although an inverse correlation with pain intensity was suggested, pointing to the potential therapeutic role of vitamin D supplementation (ref: Alonso-Pérez doi.org/10.3390/nu16234061/). Furthermore, a web-based cross-sectional study in China assessed the knowledge, attitude, and practice (KAP) of fibromyalgia patients, revealing suboptimal knowledge and moderate attitudes towards the condition, which may affect self-management and quality of life (ref: Liang doi.org/10.1186/s12889-024-21076-6/). These studies collectively emphasize the multifaceted nature of pain and its impact on the quality of life in myopathy patients, underscoring the importance of comprehensive management strategies.

Emerging technologies and methodologies are transforming the landscape of myopathy research, enabling more precise monitoring and intervention strategies. A novel wireless near-infrared sensing system, designed for continuous monitoring of laryngeal muscles, exemplifies the potential of AI-boosted technologies in neuromuscular disease management. This system allows for real-time assessment of muscle movements without the need for invasive procedures, thereby enhancing patient comfort and data accuracy (ref: Liu doi.org/10.1073/pnas.2410750121/). Additionally, the application of nailfold videocapillaroscopy (NVC) in idiopathic inflammatory myopathies has shown promise in correlating capillary abnormalities with pulmonary outcomes, suggesting that this non-invasive imaging technique can serve as a valuable tool in clinical assessments (ref: Sieiro Santos doi.org/10.1093/rheumatology/). Furthermore, a randomized controlled trial investigating the effects of priming and task-specific training for arm weakness post-stroke highlights the importance of innovative rehabilitation strategies in improving motor function (ref: King doi.org/10.1002/acn3.52271/). These advancements not only enhance our understanding of myopathies but also pave the way for personalized treatment approaches that can significantly improve patient outcomes.

The epidemiology and public health aspects of myopathies are crucial for understanding disease prevalence, risk factors, and long-term outcomes. A nationwide study assessing long-term complications following prehospital intraosseous access revealed that serious complications such as osteomyelitis and osteonecrosis occurred in less than 0.1% of cases, suggesting that this procedure is relatively safe in emergency settings (ref: Petersen doi.org/10.1016/j.resuscitation.2024.110454/). Additionally, the evaluation of task-specific training for arm weakness post-stroke in a randomized controlled trial provides insights into rehabilitation strategies that can enhance recovery and quality of life for individuals with neurological impairments (ref: King doi.org/10.1002/acn3.52271/). Furthermore, innovative approaches such as hydroxyapatite nanoparticle-mediated delivery of the dystrophin gene for Duchenne muscular dystrophy highlight the intersection of public health and advanced therapeutic strategies, aiming to address the genetic underpinnings of myopathies (ref: Kotharkar doi.org/10.1039/d4nr03906h/). These studies underscore the importance of integrating epidemiological data with emerging therapeutic technologies to inform public health policies and improve patient care in myopathy-related conditions.