Department of Gene Therapy, Saad Pharmaceuticals, Juhkentali 8, 10132 Tallinn, Estonia.
Department of Clinical and Experimental Medicine, Pisa University School of Medicine, Via Paradisa 2, 56100 Pisa, Italy.
Biomolecules. 2023 Aug 28;13(9):1319. doi: 10.3390/biom13091319.
Dystrophinopathies are x-linked muscular disorders which emerge from mutations in the gene, including Duchenne and Becker muscular dystrophy, and dilated cardiomyopathy. However, Duchenne muscular dystrophy interconnects with bone loss and osteoporosis, which are exacerbated by glucocorticoids therapy. Procedures for diagnosing dystrophinopathies include creatine kinase assay, haplotype analysis, Southern blot analysis, immunological analysis, multiplex PCR, multiplex ligation-dependent probe amplification, Sanger DNA sequencing, and next generation DNA sequencing. Pharmacological therapy for dystrophinopathies comprises glucocorticoids (prednisone, prednisolone, and deflazacort), vamorolone, and ataluren. However, angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), and β-blockers are the first-line to prevent dilated cardiomyopathy in dystrophinopathy patients. Duchenne muscular dystrophy gene therapy strategies involve gene transfer, exon skipping, exon reframing, and CRISPR gene editing. Eteplirsen, an antisense-oligonucleotide drug for skipping exon 51 from the gene, is available on the market, which may help up to 14% of Duchenne muscular dystrophy patients. There are various FDA-approved exon skipping drugs including ExonDys-51 for exon 51, VyonDys-53 and Viltolarsen for exon 53 and AmonDys-45 for exon 45 skipping. Other antisense oligonucleotide drugs in the pipeline include casimersen for exon 45, suvodirsen for exon 51, and golodirsen for exon 53 skipping. Advances in the diagnosis and therapy of dystrophinopathies offer new perspectives for their early discovery and care.
肌营养不良症是一种 X 连锁的肌肉疾病，由基因突变引起，包括杜氏肌营养不良症和贝克肌营养不良症以及扩张型心肌病。然而，杜氏肌营养不良症与骨丢失和骨质疏松症有关联，而糖皮质激素治疗会加剧这些问题。诊断肌营养不良症的方法包括肌酸激酶测定、单体型分析、Southern 印迹分析、免疫分析、多重 PCR、多重连接依赖性探针扩增、Sanger DNA 测序和下一代 DNA 测序。肌营养不良症的药物治疗包括糖皮质激素（泼尼松、泼尼松龙和地夫可特）、伐莫罗隆和依特伦。然而，血管紧张素转换酶（ACE）抑制剂、血管紧张素受体阻滞剂（ARB）和β受体阻滞剂是预防肌营养不良症患者扩张型心肌病的一线药物。杜氏肌营养不良症的基因治疗策略包括基因转移、外显子跳跃、外显子重排和 CRISPR 基因编辑。eteplirsen，一种用于跳过基因外显子 51 的反义寡核苷酸药物，已在市场上上市，可能对多达 14%的杜氏肌营养不良症患者有帮助。目前有多种经 FDA 批准的外显子跳跃药物，包括用于外显子 51 的 ExonDys-51、用于外显子 53 的 VyonDys-53 和 Viltolarsen 以及用于外显子 45 跳跃的 AmonDys-45。其他在研的反义寡核苷酸药物包括用于外显子 45 的 casimersen、用于外显子 51 的 suvodirsen 和用于外显子 53 跳跃的 golodirsen。肌营养不良症的诊断和治疗进展为其早期发现和治疗提供了新的视角。
