This study evaluates AAV9-U7 exon skipping therapy in the Dup2 mouse model of Duchenne muscular dystrophy (DMD). A single injection in adults restored up to 95% exon skipping, improving muscle structure and function. Neonatal treatment achieved 99% dystrophin-positive fibers and near-complete disease correction over six months. Findings suggest AAV9-based exon skipping provides long-lasting dystrophin restoration, supporting its potential as a clinical therapy for DMD exon 2 duplications.

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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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