Abstract：
Nemaline myopathies (NM) represent a group of clinically and genetically heterogeneous congenital muscle disorders with the common denominator of nemaline rods on muscle biopsy. NEB and ACTA1 are the most common causative genes. Currently, available treatments are supportive.
We explored experimental treatments for NM, identifying at least eleven mainly pre-clinical approaches utilizing murine and/or human muscle cells. These approaches target either i) the causative gene or associated genes implicated in the same pathway; ii) pathophysiologically relevant biochemical mechanisms such as calcium/myosin regulation of muscle contraction; iii) myogenesis; iv) other therapies that improve or optimize muscle function more generally; v) and/or combinations of the above. The scope and efficiency of these attempts is diverse, ranging from gene-specific effects to those widely applicable to all NM-associated genes.
The wide range of experimental therapies currently under consideration for NM is promising. Potential translation into clinical use requires consideration of additional factors such as the potential muscle type specificity as well as the possibility of gene expression remodeling. Challenges in clinical translation include the rarity and heterogeneity of genotypes, phenotypes, and disease trajectories, as well as the lack of longitudinal natural history data and validated outcomes and biomarkers.
We explored experimental treatments for NM, identifying at least eleven mainly pre-clinical approaches utilizing murine and/or human muscle cells. These approaches target either i) the causative gene or associated genes implicated in the same pathway; ii) pathophysiologically relevant biochemical mechanisms such as calcium/myosin regulation of muscle contraction; iii) myogenesis; iv) other therapies that improve or optimize muscle function more generally; v) and/or combinations of the above. The scope and efficiency of these attempts is diverse, ranging from gene-specific effects to those widely applicable to all NM-associated genes.
The wide range of experimental therapies currently under consideration for NM is promising. Potential translation into clinical use requires consideration of additional factors such as the potential muscle type specificity as well as the possibility of gene expression remodeling. Challenges in clinical translation include the rarity and heterogeneity of genotypes, phenotypes, and disease trajectories, as well as the lack of longitudinal natural history data and validated outcomes and biomarkers.
摘要：
UNASSIGNED：：神经肌病（NM）代表一组临床和遗传异质性的先天性肌肉疾病，在肌肉活检中具有神经棒的共同点。NEB和ACTA1是最常见的致病基因。目前可用的治疗方法是支持性的。
未经评估：我们探索了NM的实验治疗方法，鉴定至少11种主要利用鼠和/或人肌肉细胞的临床前方法。这些方法靶向i)与同一途径有关的致病基因或相关基因;ii)病理生理相关的生化机制,例如钙/肌球蛋白调节肌肉收缩;iii)肌肉发生;iv)更一般地改善或优化肌肉功能的其他疗法;v)和/或上述的组合。这些尝试的范围和效率是多种多样的,从基因特异性效应到广泛适用于所有NM相关基因的效应。
UNASSIGNED：：目前正在考虑的用于NM的广泛实验疗法是有希望的。潜在的临床应用需要考虑其他因素，例如潜在的肌肉类型特异性以及基因表达重塑的可能性。临床翻译面临的挑战包括基因型的稀有性和异质性，表型和疾病轨迹，以及缺乏纵向自然历史数据和经过验证的结果和生物标志物。
未经评估：我们探索了NM的实验治疗方法，鉴定至少11种主要利用鼠和/或人肌肉细胞的临床前方法。这些方法靶向i)与同一途径有关的致病基因或相关基因;ii)病理生理相关的生化机制,例如钙/肌球蛋白调节肌肉收缩;iii)肌肉发生;iv)更一般地改善或优化肌肉功能的其他疗法;v)和/或上述的组合。这些尝试的范围和效率是多种多样的,从基因特异性效应到广泛适用于所有NM相关基因的效应。
UNASSIGNED：：目前正在考虑的用于NM的广泛实验疗法是有希望的。潜在的临床应用需要考虑其他因素，例如潜在的肌肉类型特异性以及基因表达重塑的可能性。临床翻译面临的挑战包括基因型的稀有性和异质性，表型和疾病轨迹，以及缺乏纵向自然历史数据和经过验证的结果和生物标志物。
