Odom Guy L, Gregorevic Paul, Chamberlain Jeffrey S
Department of Neurology, Senator Paul D. Wellstone Muscular Dystrophy Cooperative Research Center, University of Washington School of Medicine, 1959 NE Pacific Street, Seattle, WA 98195-7720, USA.
Biochim Biophys Acta. 2007 Feb;1772(2):243-62. doi: 10.1016/j.bbadis.2006.09.007. Epub 2006 Sep 26.
Much progress has been made over the past decade elucidating the molecular basis for a variety of muscular dystrophies (MDs). Accordingly, there are examples of mouse models of MD whose disease progression has been halted in large part with the use of viral vector technology. Even so, we must acknowledge significant limitations of present vector systems that must be overcome prior to successful treatment of humans with such approaches. This review will present a variety of viral-mediated therapeutic strategies aimed at counteracting the muscle-wasting symptoms associated with muscular dystrophy. We include viral vector systems used for muscle gene transfer, with a particular emphasis on adeno-associated virus. Findings of several encouraging studies focusing on repair of the mutant dystrophin gene are also included. Lastly, we present a discussion of muscle compensatory therapeutics being considered that include pathways involved in the up-regulation of utrophin, promotion of cellular adhesion, enhancement of muscle mass, and antagonism of the inflammatory response. Considering the complexity of the muscular dystrophies, it appears likely that a multilayered approach tailored to a patient sub-group may be warranted in order to effectively contest the progression of this devastating disease.
在过去十年中，我们在阐明各种肌肉萎缩症（MDs）的分子基础方面取得了很大进展。因此，有一些MD小鼠模型的例子，其疾病进展在很大程度上通过使用病毒载体技术得以停止。即便如此，我们必须承认当前载体系统存在重大局限性，在使用此类方法成功治疗人类之前必须加以克服。本综述将介绍多种旨在对抗与肌肉萎缩症相关的肌肉萎缩症状的病毒介导治疗策略。我们将介绍用于肌肉基因转移的病毒载体系统，特别强调腺相关病毒。还包括了几项专注于修复突变型肌营养不良蛋白基因的令人鼓舞的研究结果。最后，我们讨论了正在考虑的肌肉补偿疗法，包括与上调抗肌萎缩蛋白、促进细胞黏附、增加肌肉质量以及拮抗炎症反应相关的途径。鉴于肌肉萎缩症的复杂性，为了有效对抗这种毁灭性疾病的进展，针对患者亚组量身定制的多层方法似乎是必要的。
