Editorial: Current Trends in Muscle Diseases and Their Treatment Strategies

Zihang GuoShoulong Deng^*

• Institute of Laboratory Animal Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

compared with general anesthesia. This review emphasized avoiding succinylcholine to prevent known anesthetic hazards such as rhabdomyolysis or hypercalcemia and highlighted the efficacy of Dantrolene for reversing malignant hyperpyrexial response to anesthesia. Porcine DMD models, which replicate the biochemical, clinical, and pathological features of human patients with accelerated disease progression and early cardiac involvement, have been instrumental in evaluating novel diagnostic tools like multispectral optoacoustic tomography (MSOT) for noninvasive disease monitoring and testing therapeutic strategies. Despite challenges like high cost, porcine model of DMD remains invaluable for optimizing therapies and diagnostics and developing personalized care strategies. Amyotrophic lateral sclerosis (ALS) is an adult-onset neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons, leading to weakness and atrophy, dysphagia or respiratory muscle palsy and remains incurable with an average survival of 2-5 years post-diagnosis. Current drugs like riluzole and edaravone offer only modest benefits. ALS is a multifactorial disease, involving oxidative stress, mitochondrial dysfunction, protein misfolding and metabolic disturbances. More than 30 ALS-related genes, including superoxide dismutase 1 (SOD1) gene, have been reported. Diagnosis of ALS relies on clinical assessments and biomarkers, such as elevated TDP-43 levels in peripheral blood mononuclear cells (PBMCs). Therapeutic strategies under investigation include metabolic interventions to restore glucose utilization in skeletal muscle. Fenili et al. provide a review and explore the potential of physical exercise as a coadjuvant therapy for ALS. While intense exercise may pose risks, moderate and tailored exercise such as swimming have shown neuroprotective effects in animal models by improving glucose metabolism, mitochondrial function, and antioxidant defense. Resistance and endurance training may enhance quality of life and slow down functional decline in human. This review underscores the need for personalized exercise protocols in ALS. Transgenic pig models such as hSOD1G93A and mSOD1-Tg pigs replicate human ALS pathology, including biomarker dynamics and metabolic dysfunction. These models have emerged as transformative tools in testing diagnostics and therapies for ALS to enhance translational relevance.Sarcopenia, an age-related syndrome characterized by progressive loss of muscle mass, strength, and function, has emerged as a critical health concern. Two representative surveys leveraging China Health and Retirement Longitudinal study (CHARLS) database revealed risk factors and predictive models in vulnerable groups and offered insights for early intervention. Yang et al. proved that sarcopenia mainly affects middle-aged and older Chinese women, closely related to age, waist, education, marriage, area, stroke, physical pain, depression, and region. They offer an effective tool to help clinicians better screen potential female patients. Qiao et al. developed a predictive model for sarcopenia risk in middle-aged and older adults with diabetes mellitus (DM) and validated a strong accuracy. Eight key predictors were identified: age, residence, BMI, diastolic blood pressure, cognitive function, activities of daily living (ADL), peak expiratory flow (PEF), and hemoglobin. This model serves as a practical tool for early identification of high-risk individuals and facilitates timely interventions to mitigate sarcopenia progression in diabetic populations. Zhong et al. employed bioinformatics and systems biology approaches to explore the shared pathogenic mechanisms between COVID-19 and sarcopenia. They identified 66 common differentially expressed genes (DEGs), including 15 hub genes. Enrichment analysis revealed functions and pathways between two diseases. Key regulators like FOXC1 and hsa-mir-155-5p were identified, and immune infiltration analysis highlighted the correlation between hub genes and immune factors. They also proposed potential therapeutic drugs and showed that valinomycin PC3 UP is the best candidate for the treatment of sarcopenia and COVID-19. Finally, they demonstrated ALDH1L2 and KLF5 showed the best diagnostic potential for COVID-19 and sarcopenia. These findings suggest shared pathways in COVID-19 and sarcopenia, offering insights for early diagnosis, effective treatment and targeted therapies.Beyond above muscle diseases, several other neuromuscular disorders present unique pathological mechanisms and therapeutic challenges. Fibrosarcoma, an aggressive and poorly soft tissue sarcoma, poses significant therapeutic challenges. Radzka et al. evaluated the potential role of natural NF-κB inhibitors in fibrosarcoma. The results showed selective cytotoxicity toward cancer cells by inducing apoptosis and indicated that CAPE, biochanin A, and CurE could inhibit actin polymerization and disrupt the cytoskeleton of cancer cells. Cellular stress and vacuolation as well as metabolic changes are more pronounced in cancer cells compared to normal cells. This research supports the effect and safety of these natural compounds with low-toxicity as anticancer agents, particularly in the treatment of fibrosarcoma. Lu et al. provide a review and explore the role of mitochondrial defects in sporadic inclusion body myositis (sIBM), a subtype of idiopathic inflammatory myopathies (IIM) with unique pathological features such as muscle inflammation, rimmed vacuoles, and protein aggregation within the myofibers. Key mitochondrial abnormalities including large-scale mitochondrial DNA deletion, aberrant protein aggregation, and slowed organelle turnover are more prominent in sIBM than in other types of IIM, indicating that nonimmune tissue dysfunction might contribute to the disease's onset as patients with sIBM are refractory to conventional immunosuppressant treatment. They also discuss potential mitochondrial-targeted therapies, such as antioxidants and mitophagy inducers like Urolithin A. Understanding mitochondrial dysfunction in sIBM could pave the way for novel treatments targeting organelle health. Spinal muscular atrophy (SMA) is an autosomal recessive genetic disorder marked by progressive, symmetrical muscle weakness and atrophy. Jieda et al. provide a case report and describe a child with initial limb hypotonia and abnormal signal changes in brain MRI. Genetic testing ultimately confirmed the diagnosis of SMA. This report highlights the rarity of brain MRI abnormalities in SMA and the importance of early intervention, which may aid early diagnosis alongside genetic testing. Pathogenic variations in gene encoding the skeletal muscle ryanodine receptor (RyR1) are associated with malignant hyperthermia (MH) and RYR1-related myopathies (RYR1-RM). R615C porcine model, the first established preclinical model, has been instrumental in understanding pathomechanisms and testing potential therapeutics like dantrolene.In addition to conventional treatment methods, recent studies demonstrate the successful generation of humanized skeletal muscle in MYF5/MYOD/MYF6-null pig embryos using blastocyst complementation with human induced pluripotent stem cells (hiPSCs). These findings offer potential of producing exogenic tissues for xenotransplantation to address challenges in muscle diseases treatment and highlight the feasibility of interspecies chimeras in regenerative medicine.In summary, the landscape of muscle disease research is rapidly evolving driven by innovations in diagnostics, targeted therapies, and preclinical models. These advances underscore the importance of multidisciplinary collaboration. While challenges such as therapeutic accessibility and complexity of disease heterogeneity remain, future efforts should focus on personalized interventions, translational research and animal models to bridge the gap between bench and bedside, ultimately offering hope for improved outcomes and enhancing the quality of life for patients worldwide.