Personal take on this article: This study evaluates the effectiveness of Nusinersen, a drug for treating spinal muscular atrophy (SMA), in adolescents and adults. The researchers conducted a systematic review and meta-analysis of 14 studies involving 539 patients aged 13–72 years, predominantly with SMA Type II or III.  Nusinersen was found to improve or stabilize motor function over 24 months. For the Hammersmith Functional Motor Scale–Expanded (HFMSE), patients showed an …

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1. Introduction: In the last 25 years, 18 oligonucleotide therapeutics have been approved for treating diseases like spinal muscular atrophy, Duchenne muscular dystrophy, and hereditary transthyretin-mediated amyloidosis. These therapies operate through different mechanisms, including antisense oligonucleotides (ASOs), splice-switching oligonucleotides (SSOs), RNA interference (RNAi), and RNA aptamers. 2. Historical Background: Oligonucleotide therapeutics trace back to the 1950s and 1960s with early discoveries in DNA and RNA synthesis. Pioneers like Todd, Khorana, …

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Personal take on this article: This paper discusses "ubiquitylomics," an emerging method for studying protein ubiquitylation in skeletal muscles. Ubiquitylation, a key post-translational modification, plays a vital role in regulating protein turnover and cellular processes, which is crucial for maintaining muscle health. The complexity of ubiquitylation presents challenges in characterizing the ubiquitylated proteins and understanding their biological significance. Ubiquitylomics leverages mass spectrometry to detect and analyze ubiquitylated proteins, providing insights …

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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: This study investigates how the knockdown of the circular RNA CDR1as affects goat skeletal muscle satellite cells (SMSCs). The researchers focused on understanding the relationship between CDR1as, miR-27a-3p, and ANGPT1 during the differentiation of these cells. They discovered that knocking down CDR1as results in upregulation of miR-27a-3p, which in turn inhibits the expression of ANGPT1, a key gene involved in muscle cell differentiation. The authors …

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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 progressive muscle deterioration. The lack of functional dystrophin causes muscle weakness, cardiac and respiratory issues, and ultimately leads to early death. Traditional treatments like corticosteroids only delay the disease progression and are associated with serious side effects. In recent years, gene and antisense therapies have emerged as …

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Personal take on this article: This paper focuses on spinal and bulbar muscular atrophy (SBMA), an adult-onset neurodegenerative disorder linked to motor neuron and skeletal muscle damage, caused by trinucleotide expansions in the androgen receptor gene. SBMA shares features with polyglutamine diseases and motor neuron disorders, affecting both the central nervous system and muscle function. The paper emphasizes nucleic acid-based therapies like antisense oligonucleotides (ASOs) and small interfering RNAs (siRNAs) …

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    Personal take on this article: This paper outlines consensus guidelines for the design and testing of antisense oligonucleotides (ASOs) specifically tailored to individual patients, known as N-of-1 therapies. ASOs are short strands of synthetic DNA that can modify gene expression by altering pre-mRNA splicing, offering potential treatments for various genetic diseases. The paper highlights the importance of designing ASOs that skip certain exons to restore protein function, which …

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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: The research article estimates the prevalence of GNE myopathy (GNEM), a rare neuromuscular disorder, using data from population genetic databases. GNEM is caused by mutations in the GNE gene and is characterized by progressive muscle atrophy. Due to underdiagnosis, current prevalence estimates range between 1 to 9 cases per million, but these are likely underestimations. This study uses allele frequencies from large genetic …

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