This open-label study evaluates casimersen and golodirsen in DMD patients with rare single exon duplications (exon 45 or 53). Over 48 weeks, dystrophin levels increased from 0.94% to 5.1%, with dystrophin-positive fibers rising from 14% to 50%. RT-PCR confirmed exon skipping, while pulmonary and cardiac functions remained stable. No major safety concerns emerged, but longer trials with larger cohorts are needed to assess long-term clinical benefits. These findings highlight exon skipping as a targeted therapy for rare DMD mutations.

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This study assesses exon 53 skipping in Duchenne muscular dystrophy (DMD) using locked nucleic acid (LNA)-modified antisense oligonucleotides (AONs) in a humanized DMD mouse model. While certain LNA-AONs (LNA-FRNA, LNA-2′OMe) achieved high exon skipping, actual dystrophin restoration was minimal due to RNA interference issues affecting cDNA synthesis. Optimizing AON designs, RNA analysis methods, and alternative exon targets is crucial for improving therapeutic efficacy in DMD exon skipping therapies.

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Rare diseases affect a small percentage of the population, with Duchenne muscular dystrophy (DMD) and cystic fibrosis as examples. Orphan diseases, however, lack adequate treatment options regardless of prevalence. While most rare diseases are orphan diseases, some common conditions like malaria can be considered orphan due to low commercial interest. Both face limited research, diagnostic challenges, and treatment barriers, requiring greater investment in drug development.

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This study advances next-generation exon 51 skipping antisense oligonucleotides (AONs) for Duchenne muscular dystrophy (DMD) by incorporating novel chemical modifications like 5-methylcytosine and locked nucleic acids (LNAs). Screening 100+ AONs identified an optimized target site, achieving 65-fold higher exon skipping and restoring 30-40% dystrophin levels in preclinical models. These AONs demonstrated improved muscle integrity, enhanced motor function, and a favorable safety profile, marking a major step toward safer, more effective DMD therapies.

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This mini-review explores ataluren therapy for nonsense mutation Duchenne muscular dystrophy (nmDMD), covering clinical guidelines and an implementation model for Sweden. Ataluren delays muscle degeneration, preserves ambulation, and improves pulmonary function in ambulatory nmDMD patients. A proposed centralized expert committee would oversee access and monitoring. Despite high costs, equitable treatment strategies aim to enhance care and outcomes for DMD patients with nonsense mutations.

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This study identifies Exosome-Binding Peptide (EBP) as a key Wnt7a secretion signal for extracellular vesicles (EVs), enabling long-range intercellular signaling. EBP binds to coatomer proteins (COPA & COPB2), anchoring Wnt7a to EVs and enhancing muscle repair. This mechanism, conserved in Wnt proteins, has implications for neuromuscular disease therapies, including Duchenne muscular dystrophy (DMD). EBP-guided EV delivery could revolutionize targeted drug and protein therapies, bypassing traditional systemic delivery challenges.

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This systematic review and meta-analysis evaluated five randomized controlled trials (RCTs) on exon-skipping therapies for Duchenne muscular dystrophy (DMD). Analyzing 322 patients, the study assessed eteplirsen and drisapersen using 6MWT and NSAA scores. Results showed no significant improvement over placebo. Drisapersen (6 mg/kg) provided minor benefits but had renal toxicity risks, while eteplirsen showed fewer side effects but lacked robust efficacy data. The study calls for long-term trials to confirm exon skipping’s clinical impact.

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Exon-skipping therapy aims to restore dystrophin production in Duchenne muscular dystrophy (DMD) by using antisense oligonucleotides (AONs) to bypass mutations. Eteplirsen and viltolarsen target exon 51, producing a truncated but functional dystrophin protein. While promising, challenges remain, including low dystrophin levels and variable patient responses. Gene therapy and stop codon read-through drugs offer alternative strategies. Early intervention and combination therapies may improve outcomes for DMD patients.

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This phase 2, open-label trial evaluated AVI-4658 (PMO) therapy in 19 boys with Duchenne muscular dystrophy (DMD), assessing exon 51 skipping and dystrophin restoration. The drug was well tolerated, showing dose-dependent dystrophin expression, with significant improvements at higher doses. Increased dystrophin correlated with protein localization and reduced inflammation, though responses varied. Findings support AVI-4658 as a potential disease-modifying treatment, emphasizing the need for long-term trials to confirm clinical benefits.

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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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