Research in this theme highlights the critical role of mitochondrial function and muscle dynamics in various myopathies. A study by Martucci demonstrated that the R107Q mutation in mitochondrial single-stranded DNA-binding protein (mtSSB) significantly impairs its ability to bind and compact ssDNA, likely disrupting mtDNA replication and leading to mitochondrial dysfunction (ref: Martucci doi.org/10.1093/nar/). Additionally, Lenardič's work on satellite cells indicates that low yields from autologous sources hinder muscle regeneration therapies for conditions like Duchenne muscular dystrophy (DMD). The study explored the potential of deriving functional muscle stem cells from allogeneic and xenogeneic hosts, which could enhance therapeutic options (ref: Lenardič doi.org/10.1172/JCI166998/). Furthermore, Bogomolovas reviewed the transition of myosin inhibitors from cardiac applications to treating skeletal muscle myopathies, emphasizing the therapeutic potential of mavacamten in managing muscle contractility (ref: Bogomolovas doi.org/10.1172/JCI179958/). In the context of Laing distal myopathy, Buvoli's research revealed that the R1500P mutation in the β-myosin rod disrupts myosin cross-bridging activity, leading to muscle fatigue and increased ATP consumption (ref: Buvoli doi.org/10.1172/JCI172599/). Phan's study on VCP pathogenic variants in multisystem proteinopathy highlighted the common pathological feature of ubiquitinated intranuclear inclusions across various tissues, linking mitochondrial dysfunction to muscle pathology (ref: Phan doi.org/10.1172/JCI169039/). Lastly, Ceron's investigation into ACTG2 mutations provided insights into the molecular mechanisms underlying visceral myopathy, revealing how specific mutations impact muscle function (ref: Ceron doi.org/10.1126/sciadv.adn6615/).

This theme focuses on the genetic and epigenetic factors contributing to myopathies, particularly facioscapulohumeral muscular dystrophy (FSHD) and Duchenne muscular dystrophy (DMD). Engal's research elucidated how the loss of SMCHD1 leads to DNMT3B splicing dysregulation, resulting in DUX4 overexpression, a key player in FSHD pathogenesis (ref: Engal doi.org/10.1126/sciadv.adn7732/). Granados investigated the role of SETDB1 in modulating TGFβ responses in DMD myotubes, revealing that TGFβ signaling is constitutively activated in DMD, contributing to muscle dysfunction (ref: Granados doi.org/10.1126/sciadv.adj8042/). Ma's study demonstrated that the exchange of subtelomeric regions between chromosomes can revert the FSHD genotype and phenotype, highlighting the potential for genetic interventions (ref: Ma doi.org/10.1126/sciadv.adl1922/). Hart's work on microdystrophin gene therapy for DMD raised concerns about the need for careful monitoring of cardiac function due to high expression levels in the heart, which could lead to adverse effects (ref: Hart doi.org/10.1172/jci.insight.165869/). Southwell's findings on CHCHD10 mutations revealed a metabolic shift in mutant mice, emphasizing the importance of metabolic pathways in mitochondrial cardiomyopathy (ref: Southwell doi.org/10.1038/s44321-024-00067-5/). Huang's comprehensive genetic analysis of FSHD using long-read sequencing techniques provided insights into the genetic heterogeneity of the disease (ref: Huang doi.org/10.1186/s12967-024-05259-8/). Lastly, Du's research on thymidine phosphorylase deficiency in MNGIE highlighted lysosomal dysfunction and its implications for mitochondrial quality control (ref: Du doi.org/10.1186/s12967-024-05275-8/).

This theme encompasses innovative therapeutic strategies for managing myopathies, particularly DMD and related conditions. Lenardič's exploration of allogeneic and xenogeneic muscle stem cell transplantation addresses the challenge of low satellite cell yields, presenting a promising avenue for regenerative therapies in muscle diseases (ref: Lenardič doi.org/10.1172/JCI166998/). Bogomolovas highlighted the successful application of myosin inhibitors, such as mavacamten, in treating skeletal muscle myopathies, showcasing their potential to improve muscle contractility and overall function (ref: Bogomolovas doi.org/10.1172/JCI179958/). De Masi's study on Cyclo His-Pro demonstrated its efficacy in attenuating muscle degeneration in murine models of DMD, suggesting a therapeutic role in reducing inflammation and fibrosis (ref: De Masi doi.org/10.1002/advs.202305927/). Hart's investigation into microdystrophin gene therapy for DMD raised critical considerations regarding cardiac expression levels, emphasizing the need for careful monitoring in clinical settings (ref: Hart doi.org/10.1172/jci.insight.165869/). Additionally, Schamne's research on caffeine's effects on central fatigue during exercise in women with fibromyalgia provides insights into non-pharmacological interventions that may enhance exercise tolerance and quality of life (ref: Schamne doi.org/10.1249/MSS.0000000000003466/).

Research in this theme delves into the inflammatory and immune mechanisms underlying myopathies. Siddiqui's study on immune checkpoint therapies revealed the molecular pathways associated with immune-related adverse events, including myocarditis and myositis, emphasizing the need for understanding immune responses in patients undergoing such treatments (ref: Siddiqui doi.org/10.1158/2326-6066.CIR-24-0011/). Southwell's findings on CHCHD10 mutations highlighted the role of metabolic rewiring and mitochondrial stress responses in the context of inflammation, suggesting that dietary interventions may mitigate disease progression (ref: Southwell doi.org/10.1038/s44321-024-00067-5/). Manning's investigation into polymyalgia rheumatica (PMR) demonstrated metabolomic alterations influenced by glucocorticoid treatment, shedding light on the persistent fatigue experienced by patients (ref: Manning doi.org/10.1016/j.jaut.2024.103260/). Zhao's genome-wide meta-analysis identified modifiable risk factors for PMR, providing potential therapeutic targets for managing this inflammatory condition (ref: Zhao doi.org/10.1093/rheumatology/). Lastly, the study by Saito on long COVID patients with chronic fatigue syndrome revealed diverse immunological dysregulation, highlighting the complex interplay between inflammation and chronic fatigue (ref: Saito doi.org/10.1016/j.jaut.2024.103267/).

This theme focuses on identifying diagnostic and prognostic factors that influence outcomes in myopathy patients. Zampogna's research on Parkinson's disease examined the predictive value of preoperative motor disability on outcomes following deep brain stimulation, providing insights into the relationship between bradykinesia, rigidity, and clinical interventions (ref: Zampogna doi.org/10.1002/ana.26961/). Mease's study on fibromyalgia prevalence in psoriatic arthritis highlighted the impact of nociplastic pain on disease severity assessments, emphasizing the need for comprehensive evaluations in rheumatologic conditions (ref: Mease doi.org/10.1002/acr.25358/). Saito's work on long COVID patients with chronic fatigue syndrome identified immunological dysregulation as a significant factor affecting patient outcomes, underscoring the importance of tailored management strategies (ref: Saito doi.org/10.1016/j.jaut.2024.103267/). Chow's investigation into anti-HMGCR myopathy revealed significant differences in incidence rates between Polynesian and European populations, highlighting the need for population-specific diagnostic considerations (ref: Chow doi.org/10.1093/rheumatology/). These studies collectively underscore the importance of understanding the multifaceted nature of myopathies to improve diagnostic accuracy and prognostic predictions.

Research in this theme explores the underlying pathophysiological mechanisms contributing to various myopathies. Bogomolovas's review on myosin inhibitors illustrates how targeting myosin ATPase activity can mitigate hypercontractility in myopathies, providing a novel therapeutic approach (ref: Bogomolovas doi.org/10.1172/JCI179958/). Lenardič's study on satellite cells emphasizes their regenerative potential and the challenges posed by low yields in autologous transplants, suggesting that allogeneic or xenogeneic sources may enhance therapeutic outcomes (ref: Lenardič doi.org/10.1172/JCI166998/). Southwell's findings on CHCHD10 mutations reveal a metabolic shift in mutant mice, indicating that mitochondrial dysfunction plays a critical role in disease progression (ref: Southwell doi.org/10.1038/s44321-024-00067-5/). Huang's genetic analysis of FSHD highlights the complexity of the disease's pathophysiology, revealing significant genetic heterogeneity that complicates diagnosis and treatment (ref: Huang doi.org/10.1186/s12967-024-05259-8/). Du's research on thymidine phosphorylase deficiency in MNGIE underscores the impact of lysosomal dysfunction on mitochondrial quality control, linking metabolic disturbances to muscle pathology (ref: Du doi.org/10.1186/s12967-024-05275-8/). Collectively, these studies enhance our understanding of the intricate pathophysiological networks involved in myopathies.

This theme addresses the clinical outcomes and quality of life issues faced by patients with myopathies. Lenardič's exploration of satellite cell transplantation highlights the potential for improved muscle regeneration and function, which could significantly enhance the quality of life for patients with conditions like DMD (ref: Lenardič doi.org/10.1172/JCI166998/). Mease's study on fibromyalgia prevalence in psoriatic arthritis emphasizes the need for comprehensive pain management strategies, as the presence of fibromyalgia can complicate disease severity assessments and affect overall patient well-being (ref: Mease doi.org/10.1002/acr.25358/). Saito's research on long COVID patients with chronic fatigue syndrome reveals the profound impact of chronic symptoms on quality of life, highlighting the need for targeted interventions to address these debilitating effects (ref: Saito doi.org/10.1016/j.jaut.2024.103267/). Schamne's findings on caffeine's effects on central fatigue during exercise suggest that dietary interventions may play a role in improving exercise tolerance and quality of life for individuals with fibromyalgia (ref: Schamne doi.org/10.1249/MSS.0000000000003466/). Collectively, these studies underscore the importance of addressing both clinical outcomes and quality of life considerations in the management of myopathy patients.

Research in this theme focuses on the epidemiological aspects and population-specific factors influencing myopathies. Lenardič's study on satellite cells highlights the challenges of low yields in autologous transplants, which may vary across populations, emphasizing the need for tailored approaches in regenerative therapies for muscle diseases like DMD (ref: Lenardič doi.org/10.1172/JCI166998/). Mease's investigation into fibromyalgia prevalence in psoriatic arthritis reveals that this condition affects a significant proportion of patients, suggesting that awareness and screening for fibromyalgia should be integrated into routine care for rheumatologic diseases (ref: Mease doi.org/10.1002/acr.25358/). Saito's research on long COVID patients with chronic fatigue syndrome highlights the diverse immunological responses observed in different populations, indicating that genetic and environmental factors may influence disease severity and outcomes (ref: Saito doi.org/10.1016/j.jaut.2024.103267/). Chow's study on anti-HMGCR myopathy underscores the disparities in incidence rates between Polynesian and European populations, suggesting that genetic predispositions may play a critical role in the epidemiology of this condition (ref: Chow doi.org/10.1093/rheumatology/). These findings collectively emphasize the importance of considering population-specific factors in the diagnosis, treatment, and management of myopathies.