1. Background and Purpose: Antisense oligonucleotide (AO)-mediated exon skipping is a promising strategy for treating genetic disorders like Duchenne Muscular Dystrophy (DMD). This method alters dystrophin pre-mRNA splicing to create a shorter but functional protein, potentially converting severe DMD into a milder Becker Muscular Dystrophy (BMD) phenotype. The paper highlights the significance of skipping exons 45–55, a common mutation area that could help nearly half of DMD patients.   2. …

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Casimersen (AMONDYS 45™) is a therapeutic antisense oligonucleotide designed for patients with Duchenne Muscular Dystrophy (DMD) whose gene mutation is amenable to exon 45 skipping. DMD is a genetic disorder characterized by the absence of dystrophin, a crucial protein for muscle function. This results in progressive muscle degeneration and loss of mobility, eventually affecting the heart and lungs. Casimersen works by binding to the mutated pre-mRNA, skipping exon 45 to …

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This paper introduces a novel therapeutic approach for Duchenne Muscular Dystrophy (DMD) using NS-089/NCNP-02, an antisense oligonucleotide (ASO) designed to skip exon 44 of the dystrophin gene. DMD is a severe muscle disorder caused by mutations in the DMD gene, leading to a lack of dystrophin protein. Exon skipping helps to restore the reading frame of dystrophin, enabling the production of a shorter but functional dystrophin protein. The authors focused …

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Duchenne Muscular Dystrophy (DMD) is a severe genetic disorder affecting males, characterized by muscle degeneration and early death. Antisense-mediated exon skipping therapy offers a new hope by producing a truncated but functional dystrophin protein. Casimersen (Amondys 45) specifically targets exon 45 of the dystrophin gene, which applies to about 8% of DMD patients. The drug was approved by the FDA in 2021, based on its promising preclinical and phase I/II …

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The paper presents findings from a phase 3 clinical trial (EMBARK) evaluating the efficacy and safety of a gene therapy, delandistrogene moxeparvovec, in patients with Duchenne muscular dystrophy (DMD). DMD is a severe, inherited condition that progressively weakens muscles due to the absence of dystrophin. The therapy uses an AAV vector to deliver a functional dystrophin gene into muscle cells. The trial involved boys aged 4 to 8, who were …

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This study focuses on translating microarray findings from golden retriever muscular dystrophy (GRMD) to identify biomarkers that could reflect cardiac and skeletal muscle function in Duchenne muscular dystrophy (DMD) patients. Since DMD affects both cardiac and skeletal muscle function, identifying molecular differences between these tissues can help predict disease progression. The research utilized GRMD models, which closely mimic DMD in humans, and studied gene expression in the left ventricle (LV) …

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Duchenne Muscular Dystrophy (DMD) is a rare genetic disorder characterized by progressive muscle degeneration, often leading to severe cardiac complications. This systematic review aimed to analyze and grade the available literature on predictors of cardiac disease in DMD patients. The researchers reviewed studies published from 2000 to 2022, involving 9,232 patients across 33 publications. The focus was on pharmacological treatments and genetic mutations that influence heart health in DMD patients, …

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Personal take on this article: Duchenne Muscular Dystrophy (DMD) is a severe genetic disorder caused by mutations in the dystrophin gene, leading to muscle degeneration and weakness. In recent years, exon skipping therapy has emerged as a promising molecular treatment. This approach uses antisense oligonucleotides (AONs) to skip specific exons during the mRNA splicing process, helping to restore the reading frame and produce a functional, albeit truncated, dystrophin protein. This …

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    Personal take on this article: The paper provides a comprehensive set of guidelines for designing antisense oligonucleotides (AONs) with a focus on splice modulation. AONs are tools used to interfere with gene expression by targeting specific mRNA sequences, either to degrade them, block translation, or modify splicing. This study particularly focuses on the latter, using AONs to induce exon skipping in the dystrophin gene, which has therapeutic potential …

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      Personal take on this article: This study evaluates the safety, tolerability, and pharmacokinetics of eteplirsen in boys aged 6 to 48 months with Duchenne muscular dystrophy (DMD) amenable to exon 51 skipping. Eteplirsen, a phosphorodiamidate morpholino oligomer (PMO), is designed to restore dystrophin production. The open-label, dose-escalation trial involved 15 boys divided into two cohorts: one group aged 24 to 48 months and another aged 6 to …

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