揭示杜兴氏肌肉萎缩症的胚胎起源。

IF 4.6 3区 医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL WIREs Mechanisms of Disease Pub Date : 2024-10-23 DOI:10.1002/wsbm.1653
Philip Barrett, Ke'ale W Louie, Jean-Baptiste Dupont, David L Mack, Lisa Maves
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引用次数: 0

摘要

杜氏肌营养不良症(DMD)是一种严重的退行性肌肉疾病,由编码肌营养不良蛋白的 DMD 基因突变引起。尽管法国神经学家纪尧姆-杜兴-德-布洛涅(Guillaume Duchenne de Boulogne)在 19 世纪末首次描述了这种疾病,并在 20 世纪 80 年代确定了导致 DMD 的基因突变,但治疗方法仍然充满挑战。目前的标准疗法是皮质类固醇治疗,这种疗法可延缓肌肉功能障碍的发展,但会产生严重的不良反应。包括 AAV 介导的基因转移、CRISPR 基因编辑和小分子干预在内的新兴治疗方法正在开发中,但面临着相当大的障碍。虽然 DMD 被认为是一种进行性肌肉疾病,但在胎儿肌肉形成过程中,肌肉损伤和异常分子特征就已显现。这种早期发病的病理现象表明,目前的疗法之所以收效甚微,部分原因可能是这些疗法是在缺乏肌营养不良蛋白的情况下,在胚胎肌生成发生异常后才开始使用的。因此,确定 DMD 的最佳治疗策略和干预窗口可能取决于更好地了解 DMD 最早的发病机制。随着新技术的应用,该领域对 DMD 早期肌肉发育异常的了解越来越详细。全面了解 DMD 发病和进展的初始事件将有助于产生和测试有效的治疗干预措施。
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Uncovering the Embryonic Origins of Duchenne Muscular Dystrophy.

Duchenne muscular dystrophy (DMD) is a severe degenerative muscle disease caused by mutations in the DMD gene, which encodes dystrophin. Despite its initial description in the late 19th century by French neurologist Guillaume Duchenne de Boulogne, and identification of causal DMD genetic mutations in the 1980s, therapeutics remain challenging. The current standard of care is corticosteroid treatment, which delays the progression of muscle dysfunction but is associated with significant adverse effects. Emerging therapeutic approaches, including AAV-mediated gene transfer, CRISPR gene editing, and small molecule interventions, are under development but face considerable obstacles. Although DMD is viewed as a progressive muscle disease, muscle damage and abnormal molecular signatures are already evident during fetal myogenesis. This early onset of pathology suggests that the limited success of current therapies may partly be due to their administration after aberrant embryonic myogenesis has occurred in the absence of dystrophin. Consequently, identifying optimal therapeutic strategies and intervention windows for DMD may depend on a better understanding of the earliest DMD disease mechanisms. As newer techniques are applied, the field is gaining increasingly detailed insights into the early muscle developmental abnormalities in DMD. A comprehensive understanding of the initial events in DMD pathogenesis and progression will facilitate the generation and testing of effective therapeutic interventions.

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WIREs Mechanisms of Disease
WIREs Mechanisms of Disease MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
11.40
自引率
0.00%
发文量
45
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