This study investigates how voluntary exercise impacts AAV-U7-mediated exon skipping therapy in D2-mdx mice with Duchenne muscular dystrophy (DMD). Exercise did not worsen muscle damage or reduce viral genome expression, though dystrophin-positive muscle area declined from 80% to 65%. Despite this, gene therapy remained effective, and muscle strength improved. Findings suggest exercise can be integrated into DMD treatments without major therapy disruption, though long-term effects need further study.

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This study explores antisense oligonucleotide (AON) therapy to correct cryptic pre-mRNA splicing defects in Pompe disease. Pathogenic variants in the GAA gene lead to aberrant splice site activation, disrupting enzyme production. Researchers developed a splicing assay to detect defects in patient-derived fibroblasts and successfully redirected cryptic splicing back to canonical sites, improving GAA enzyme activity. This personalized approach offers a promising alternative to enzyme replacement therapy for adult-onset Pompe disease.

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This study explores direct reprogramming of DMD fibroblasts into myotubes as a non-invasive model for testing antisense oligonucleotide (AO)-mediated exon skipping. Using MyoD gene induction, researchers converted fibroblasts into muscle cells, then applied phosphorodiamidate morpholino oligomers (PMOs) to skip exons 45–55, restoring dystrophin expression. This scalable, reproducible method provides an alternative to muscle biopsies, advancing DMD drug development.

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Introducing JIF Hub, a powerful platform for researchers to access Journal Impact Factors (JIF) and key journal metrics. Developed by Saber SamadiAfshar (Afshar Research Group), JIF Hub simplifies journal selection with features like ISSN search, impact factor trends (2020-2023), total citations, quartile rankings, and open-access insights. Designed for researchers, students, and administrators, JIF Hub helps optimize publication decisions and research visibility efficiently.

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Antisense oligonucleotides (ASOs) struggle with endosomal entrapment and inefficient nuclear localization, limiting their therapeutic impact. Researchers explore solutions like endosomal escape agents, peptide-based transport, lipid nanoparticles (LNPs), and nuclear localization signals (NLS) to enhance delivery. Combining non-toxic endosomal escape mechanisms with NLS-enhanced strategies could significantly improve ASO therapies, making them more effective for disease treatment.

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Antisense oligonucleotides (ASOs) are promising gene-targeting therapies, but endosomal escape and nuclear localization limit their effectiveness. Only 1-2% of ASOs reach their target mRNA. Strategies like lipid nanoparticles, pH-responsive materials, and membrane-destabilizing agents aim to improve ASO delivery. Enhancing nuclear localization is also critical for splice-switching oligonucleotides (SSOs). Overcoming these barriers is essential for making ASO-based therapies viable in clinical settings.

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This study evaluates DUX4-targeting antisense oligonucleotide (ASO) therapy for facioscapulohumeral muscular dystrophy (FSHD). Systemic ASO delivery in an FSHD mouse model reduced DUX4 expression, alleviated inflammation and fibrosis, and prevented activation of DUX4 target genes. However, it did not fully restore muscle strength or prevent muscle mass loss. While promising, further optimization of ASO delivery and efficacy is needed for better therapeutic outcomes, especially if applied early in disease progression.

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Casimersen (AMONDYS 45™) is an FDA-approved antisense oligonucleotide therapy for Duchenne muscular dystrophy (DMD) patients whose mutations allow exon 45 skipping. This treatment increases dystrophin production, stabilizing muscle function. Approved in 2021, Casimersen has shown promising results in the ESSENCE trial, significantly boosting dystrophin levels. While it is not a cure, this therapy offers hope for approximately 8% of DMD patients with exon 45 mutations. Clinical trials continue to assess long-term benefits and potential side effects, particularly concerning kidney health.

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This article breaks down important terms frequently encountered in neuromuscular research. Learn about Propensity Score Matching, a statistical method for balancing groups in studies; North Star Ambulatory Assessment (NSAA) for evaluating motor function in DMD; Sarcoglycanopathy, a type of limb-girdle muscular dystrophy; Cross-sectional Studies, which analyze data at a single point in time; and Bulbar Palsy, a condition affecting speech and swallowing in diseases like ALS. These definitions help readers navigate neuromuscular research with confidence.

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This post introduces NS-089/NCNP-02, a novel exon-skipping therapy for Duchenne muscular dystrophy (DMD). Designed to target exon 44, this antisense oligonucleotide improves dystrophin restoration in DMD patients. Unlike traditional single-target ASOs, NS-089/NCNP-02 skips two different sequences within exon 44, enhancing efficiency. Studies in patient-derived cells and cynomolgus monkeys confirm its ability to induce exon skipping in both skeletal and cardiac muscle, offering a promising systemic therapy for DMD.

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