Mitochondrial myopathies and genetic disorders encompass a range of conditions characterized by dysfunction in mitochondrial DNA (mtDNA) and associated pathways. A significant advancement in this field is the development of engineered mitoARCUS nucleases, which efficiently eliminate MELAS-associated m.3243G mutant mtDNA while preserving wild-type genomes, thus shifting mtDNA heteroplasmy favorably (ref: Shoop doi.org/10.1038/s42255-023-00932-6/). This approach addresses the limitations of existing technologies by leveraging the small size and high specificity of ARCUS nucleases. In another study, a novel missense G376V-TDP-43 variant was identified in patients with late-onset distal myopathy, highlighting the diverse genetic underpinnings of muscle disorders and distinguishing them from amyotrophic lateral sclerosis (ref: Zibold doi.org/10.1093/brain/). Furthermore, biallelic NUDT2 variants were linked to a neurodevelopmental disease, emphasizing the impact of RNA processing defects on neurological health (ref: Husain doi.org/10.1093/brain/). The exploration of mitochondrial DNA depletion syndrome caused by FBXL4 mutations revealed that excessive mitophagy is a key driver of the disease, suggesting potential therapeutic strategies targeting this pathway (ref: Gao doi.org/10.1016/j.molmed.2023.11.017/). Lastly, the creation of a self-organizing neuromuscular junction model from human pluripotent stem cells offers a promising platform for studying neuromuscular diseases and testing therapeutic interventions (ref: Urzi doi.org/10.1038/s41467-023-43781-3/).

Inflammatory myopathies, particularly polymyalgia rheumatica (PMR) and dermatomyositis (DM), have garnered attention for their complex pathophysiology and management challenges. A study investigating senescent cells in giant cell arteritis (GCA) revealed an inflammatory phenotype that contributes to tissue injury via IL-6-dependent pathways, underscoring the role of cellular senescence in age-related inflammatory conditions (ref: Veroutis doi.org/10.1136/ard-2023-224467/). Additionally, new international recommendations for early referral of individuals with suspected PMR were established, aiming to enhance early diagnosis and treatment (ref: Keller doi.org/10.1136/ard-2023-225134/). The prognostic role of interferon-λ3 in anti-MDA5-positive DM-associated interstitial lung disease was highlighted, with elevated serum levels correlating with disease severity (ref: Fukada doi.org/10.1002/art.42785/). Furthermore, the presence of additional autoantibodies in juvenile-onset dermatomyositis was linked to less severe muscle disease, suggesting a nuanced relationship between autoantibody profiles and clinical outcomes (ref: Sherman doi.org/10.1002/art.42768/). Lastly, a study on the human intestinal DNA virome in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) provided insights into viral contributions to disease states, potentially informing future therapeutic strategies (ref: Hsieh doi.org/10.3390/ijms242417267/).

Research into muscle regeneration and repair mechanisms has revealed critical insights into therapeutic strategies for muscle injuries and degenerative conditions. A study demonstrated that repletion of Maresin 1 significantly improves muscle regeneration following volumetric muscle loss, indicating the importance of lipid mediators in modulating inflammation and fibrosis during recovery (ref: Castor-Macias doi.org/10.7554/eLife.86437/). In the context of X-linked myotubular myopathy, gene replacement therapy with resamirigene bilparvovec showed promising results, with muscle biopsies indicating significant improvements in myofiber size and organelle localization after treatment (ref: Lawlor doi.org/10.1016/j.ebiom.2023.104894/). Additionally, the compound BIO101 was found to stimulate myoblast differentiation and enhance muscle function in both adult and aged mice, suggesting its potential as a therapeutic agent for muscle wasting diseases (ref: Serova doi.org/10.1002/jcsm.13326/). Conversely, a study on obesity's impact on mitochondrial quality control in cancer cachexia revealed that obesity does not confer protection against muscle wasting, challenging previous assumptions about the relationship between obesity and cachexia (ref: Cardaci doi.org/10.1002/jcsm.13391/). Lastly, the role of DBC1 in maintaining skeletal muscle integrity was highlighted, with findings suggesting its involvement in myogenesis and prevention of myofiber wasting (ref: Liang doi.org/10.1002/jcsm.13398/).

Duchenne muscular dystrophy (DMD) remains a focal point of research due to its severe implications and the need for effective therapies. A study investigating dysregulated iron homeostasis in dystrophin-deficient cardiomyocytes identified potential corrective strategies through gene editing and pharmacological treatment, providing insights into the molecular mechanisms underlying DMD-associated cardiomyopathy (ref: Andrysiak doi.org/10.1093/cvr/). Additionally, the replenishment of NAD was explored as a therapeutic avenue, with gene therapy approaches showing promise in partially restoring dystrophin expression and mitigating muscle degeneration (ref: Cardoso doi.org/10.1186/s13395-023-00328-w/). The development of optimized AAV vectors for muscle gene therapy was also highlighted, addressing safety concerns associated with earlier generations of AAV vectors (ref: Shoti doi.org/10.1016/j.omtm.2023.101147/). Furthermore, the slow-release adiponectin analog ALY688-SR was shown to modify early-stage disease development in DMD, indicating a potential new therapeutic target (ref: Bellissimo doi.org/10.1152/ajpcell.00638.2023/). Lastly, insights into heart failure with preserved ejection fraction in DMD patients were provided, emphasizing the need for comprehensive management strategies in this population (ref: Teramoto doi.org/10.1016/j.jacasi.2023.06.007/).

The role of exercise and rehabilitation in managing muscle disorders has been extensively studied, revealing both benefits and challenges. An umbrella review highlighted the impact of exercise prescription variables on outcomes in musculoskeletal pain, indicating that optimal exercise strategies remain poorly defined despite their recognized benefits (ref: Arora doi.org/10.1007/s40279-023-01966-2/). In professional rugby union, a systematic review and meta-analysis assessed real-world fatigue testing, finding small decreases in performance metrics post-match, which underscores the need for effective recovery strategies (ref: Grainger doi.org/10.1007/s40279-023-01973-3/). Additionally, serum ferritin levels emerged as a significant biomarker for patients with idiopathic inflammatory myopathy-associated interstitial lung disease, suggesting that monitoring these levels could aid in prognosis and treatment decisions (ref: He doi.org/10.1016/j.semarthrit.2023.152350/). A randomized controlled trial evaluated the effectiveness of an online multicomponent program for chronic fatigue syndrome, demonstrating significant improvements in fatigue management compared to standard treatment (ref: Serrat doi.org/10.1037/hea0001346/). Lastly, a randomized crossover trial examined tailored versus generic self-management strategies for persistent fatigue in adolescents, providing insights into the effectiveness of personalized interventions (ref: Vroegindeweij doi.org/10.1111/bjhp.12711/).

Research on neuromuscular junction disorders, particularly myasthenia gravis, has advanced significantly with new therapeutic approaches. A Phase 2a trial of subcutaneous batoclimab in generalized myasthenia gravis demonstrated its safety and tolerability, alongside promising changes in immunoglobulin levels and anti-acetylcholine receptor antibodies (ref: Nowak doi.org/10.1002/acn3.51946/). This trial marks a critical step in exploring targeted therapies for this debilitating condition. Additionally, the lived experiences of individuals with fibromyalgia-related dysphagia were documented, shedding light on the psychosocial impacts of swallowing difficulties in this population (ref: Gilheaney doi.org/10.1111/hex.13932/). The structural analysis of the D290V mutant of hnRNPA2 provided insights into the molecular mechanisms affecting phase separation and aggregation, which may have implications for understanding neuromuscular diseases (ref: Lu doi.org/10.1016/j.jbc.2023.105531/). Furthermore, pathogenic variants in the DPAGT1 gene were linked to limb-girdle congenital myasthenic syndrome, revealing the complex genetic landscape of neuromuscular disorders (ref: Brande doi.org/10.1111/nan.12952/).

Pain and fatigue are critical components in the management of musculoskeletal disorders, with recent studies highlighting their complex interplay. A study examining the effects of long-chain omega-3 fatty acid supplementation on exercise-induced muscle damage found that both EPA and DHA improved recovery compared to placebo, suggesting potential dietary interventions for muscle health (ref: Heileson doi.org/10.1249/MSS.0000000000003332/). In the context of post-COVID-19 fatigue, insomnia severity was found to be significantly high, indicating a need for targeted interventions to address sleep disturbances in this population (ref: Rauwerda doi.org/10.1016/j.jpsychores.2023.111522/). The influence of transcutaneous electrical nerve stimulation (TENS) on pain thresholds in fibromyalgia patients was evaluated, revealing no significant changes in pain modulation, which raises questions about the efficacy of TENS in this context (ref: Berardi doi.org/10.1016/j.jpain.2023.12.009/). Additionally, a joint statement on early detection of interstitial lung disease in rheumatic diseases emphasized the importance of multidisciplinary approaches to improve patient outcomes (ref: Morais doi.org/10.1016/j.pulmoe.2023.11.007/). Lastly, mechanochemical studies on myopathy-linked mutations in tropomyosin provided insights into the molecular basis of muscle contractility, contributing to our understanding of muscle disorders (ref: Küçükdogru doi.org/10.1096/fj.202301604R/).

Clinical and diagnostic advances in myopathies have focused on identifying biomarkers and improving management strategies. A study on growth differentiation factor 15 (GDF-15) suggested its potential as a biomarker for disease activity in juvenile dermatomyositis, which could enhance treatment decision-making and monitoring (ref: Duvvuri doi.org/10.1093/rheumatology/). Additionally, a randomized controlled trial evaluated the necessity of stretching in managing spasticity in multiple sclerosis, challenging existing clinical practices and suggesting alternative approaches (ref: Hugos doi.org/10.1177/13524585231215960/). The prevalence of musculoskeletal co-morbidities in transthyretin amyloid cardiomyopathy was systematically reviewed, confirming significant associations that may inform clinical management (ref: Formiga doi.org/10.1002/ehf2.14622/). Furthermore, the interaction between DMD and insulin resistance was explored, highlighting the metabolic implications of dystrophin deficiency and its potential impact on disease progression (ref: Krishna doi.org/10.1249/JES.0000000000000328/). Lastly, a study on the diagnostic utility of imaging techniques in myopathies provided insights into the effectiveness of various modalities in identifying disease characteristics (ref: Allard doi.org/10.1007/s00259-023-06557-x/).