Recent advancements in genetic manipulation of mitochondrial DNA (mtDNA) have opened new avenues for addressing mitochondrial myopathies. One significant study engineered mtDNA deletions in human cells by co-expressing end-joining machinery and targeted endonucleases, overcoming previous challenges in reconstituting mtDNA deletions associated with these disorders (ref: Fu doi.org/10.1016/j.cell.2025.02.009/). Another study highlighted the role of small nucleolar RNAs (snoRNAs) in muscle differentiation, demonstrating that loss-of-function mutations in snoRNAs such as SNORA40 and SNORA70 impair myogenic differentiation in myotonic dystrophy type 1 (DM1) cells (ref: Bogard doi.org/10.1093/nar/). Furthermore, research utilizing urinary extracellular vesicles revealed disordered renal metabolism in DM1, identifying downregulated transcripts linked to metabolic dysfunction, which could provide insights into the systemic effects of the disease (ref: Kumari doi.org/10.1038/s41467-025-56479-5/). A mechanism-based approach for designing patient-specific therapies for nonsense mutation diseases was also explored, emphasizing the need for effective treatments for premature termination codon (PTC) diseases (ref: Bhat doi.org/10.1093/nar/). Lastly, a comprehensive mapping of genetic variants in the thyroid hormone transporter MCT8 provided insights into disease severity and therapeutic effectiveness, highlighting the potential for integrating genomic data with clinical outcomes (ref: Groeneweg doi.org/10.1038/s41467-025-56628-w/).

Duchenne muscular dystrophy (DMD) research has seen promising developments in therapeutic strategies aimed at improving muscle function and mitigating disease progression. One notable study demonstrated that systemic administration of MyoAAV-UA significantly upregulated endogenous full-length utrophin in mdx mice, leading to improved skeletal muscle function and reduced heart function deterioration (ref: Wu doi.org/10.1038/s41467-025-57831-5/). Inhibiting EZH2 was shown to complement glucocorticoid effects in DMD, suggesting a potential avenue for enhancing existing treatments (ref: Jeon doi.org/10.1126/sciadv.adr4443/). The development of a single-cut gene therapy model in rhesus monkeys has accelerated the generation of animal models that closely replicate human DMD pathology, facilitating the evaluation of therapeutic efficacy (ref: Bai doi.org/10.1016/j.xcrm.2025.102037/). Additionally, engineered human myogenic cells delivered via hydrogels demonstrated the ability to generate vascularized myofibers in dystrophic mouse muscle, showcasing a novel transplantation strategy (ref: Kowala doi.org/10.1016/j.xcrm.2025.102019/). Research also highlighted the under-recognized complications of inflammatory arthritis, such as periarticular myositis and muscle fibrosis, which may complicate DMD (ref: Day doi.org/10.1172/jci.insight.179928/). Lastly, long-term preservation of muscle function through repeated administration of cardiosphere-derived cells was investigated, revealing significant benefits in mdx mice (ref: Rogers doi.org/10.1016/j.stemcr.2025.102468/).

Research into myotonic dystrophy and related disorders has revealed critical insights into disease mechanisms and potential therapeutic targets. A study identified the role of small nucleolar RNAs (snoRNAs) in promoting muscle differentiation, with findings indicating that loss-of-function mutations in snoRNAs like SNORA40 and SNORA70 impair myogenic differentiation in myotonic dystrophy type 1 (DM1) (ref: Bogard doi.org/10.1093/nar/). Additionally, analysis of urinary extracellular vesicles in DM1 uncovered disordered renal metabolism, highlighting the downregulation of key metabolic transcripts, which may contribute to the systemic effects of the disorder (ref: Kumari doi.org/10.1038/s41467-025-56479-5/). In myotonic dystrophy type 2 (DM2), a novel therapeutic intervention was explored through the inhibition of TDP1, which showed promise in ameliorating muscle degeneration and improving motor functions in a Drosophila model (ref: Zhu doi.org/10.1038/s44321-025-00217-3/). Furthermore, a study on juvenile dermatomyositis (JDM) utilized tape strip expression profiling to uncover mitochondrial dysfunction as a contributing factor to disease endotypes, providing insights into the molecular mechanisms underlying skin inflammation in JDM (ref: Turnier doi.org/10.1172/jci.insight.179875/). Collectively, these studies underscore the importance of understanding the molecular underpinnings of myotonic dystrophy and related disorders to inform future therapeutic strategies.

Research on peripheral neuropathies and muscle disorders has identified key genetic factors and mechanisms underlying disease pathology. A study on GARS1-associated peripheral neuropathy revealed that specific mutations in cytosolic aminoacyl-tRNA synthetase genes lead to degeneration of peripheral motor and sensory axons, with certain variants inducing neuropathy while others do not (ref: Mora doi.org/10.1093/nar/). Additionally, heterozygous loss-of-function variants in SPTAN1 were linked to early childhood onset distal myopathy, with evidence from 14 families supporting this association (ref: De Winter doi.org/10.1016/j.gim.2025.101399/). Investigations into limb-girdle muscular dystrophy R8 (LGMD R8) highlighted the need for understanding genotype-phenotype correlations, particularly how missense variants in the TRIM32 gene affect clinical severity and protein function (ref: Liang doi.org/10.1186/s40478-025-01971-8/). These findings emphasize the importance of genetic screening and characterization in understanding the diverse manifestations of peripheral neuropathies and muscle disorders, paving the way for targeted therapeutic approaches.

Idiopathic inflammatory myopathies (IIM) research has focused on characterizing disease subtypes and improving diagnostic criteria. A multicenter retrospective cohort study validated the 2017 EULAR/ACR classification criteria for IIM in patients with anti-MDA5 antibody-positive interstitial lung disease, finding no significant differences in clinical characteristics or prognoses between patients meeting and not meeting the criteria (ref: Chen doi.org/10.1016/j.semarthrit.2025.152700/). Furthermore, nailfold videocapillaroscopy findings were associated with different IIM subtypes and interferon activation, revealing correlations between capillary abnormalities and cytokine profiles (ref: Tang doi.org/10.1186/s13075-025-03532-9/). Additionally, a study on exercise-induced muscle injury in muscular dystrophies identified a universal proteomic signature, highlighting common circulating proteins elevated in response to exercise across various myopathies (ref: Stemmerik doi.org/10.1002/acn3.70035/). These studies collectively enhance our understanding of IIM, emphasizing the need for refined diagnostic criteria and the exploration of shared molecular pathways.

The landscape of therapeutic approaches and drug development for neuromuscular disorders is rapidly evolving, with innovative strategies being explored. A multicriteria decision analysis (MCDA) framework was applied to develop candidate classification criteria for antisynthetase syndrome, demonstrating high diagnostic accuracy when tested against real-world data (ref: Zanframundo doi.org/10.1016/j.ard.2025.01.050/). In fibromyalgia, a randomized controlled trial assessed the efficacy of repetitive transcranial magnetic stimulation (rTMS) as an add-on therapy, revealing significant improvements in patient outcomes (ref: Silva doi.org/10.1016/j.bja.2024.12.045/). Additionally, research on the role of mitochondria isolated from bone mesenchymal stem cells showed promise in restraining muscle disuse atrophy and fatty infiltration following rotator cuff tears, indicating potential therapeutic applications (ref: Shi doi.org/10.1177/03635465251323001/). Furthermore, studies investigating the impact of smoking status and vascular risk factors on disability in AQP4-NMOSD and MOGAD highlighted the need for personalized treatment approaches (ref: Chan doi.org/10.1177/13524585251325069/). These findings underscore the importance of integrating novel therapeutic strategies and understanding patient-specific factors in the development of effective treatments.

Research on muscle function and rehabilitation has focused on optimizing therapeutic interventions for muscle-related disorders. An umbrella review evaluated various physical therapies for delayed-onset muscle soreness, revealing a substantial body of evidence, albeit from predominantly low-quality systematic reviews (ref: Wiecha doi.org/10.1007/s40279-025-02187-5/). Additionally, the use of mitochondria isolated from bone mesenchymal stem cells demonstrated effectiveness in mitigating muscle disuse atrophy and fatty infiltration after rotator cuff tears, suggesting a novel approach to rehabilitation (ref: Shi doi.org/10.1177/03635465251323001/). Furthermore, a longitudinal study assessed patient-reported outcomes for pexidartinib in tenosynovial giant cell tumors, indicating continued benefits from treatment over time (ref: Dai doi.org/10.1093/oncolo/). These studies highlight the significance of tailored rehabilitation strategies and the integration of innovative therapies to enhance muscle function and recovery.

The exploration of genetic variants and their implications for disease mechanisms has provided critical insights into various neuromuscular disorders. A study on the NALCN channelosome revealed that pathogenic variants influence neurodevelopmental outcomes, with loss-of-function variants correlating with more severe clinical presentations (ref: Parra-Díaz doi.org/10.1212/WNL.0000000000213429/). Additionally, research on heterozygous Duchenne muscular dystrophy mutations in females found no correlation between X inactivation patterns and muscular involvement severity, challenging previous assumptions about carrier status (ref: Riguzzi doi.org/10.1007/s00415-025-12987-4/). Furthermore, a missense variant in the EMD gene was associated with isolated dilated cardiomyopathy, expanding the understanding of EMD-related phenotypes beyond muscular dystrophy (ref: Bulmer doi.org/10.1038/s41431-025-01827-8/). These findings underscore the importance of genetic characterization in elucidating disease mechanisms and informing potential therapeutic strategies.