Geel T M, McLaughlin P M J, de Leij L F M H, Ruiters M H J, Niezen-Koning K E
Department of Pathology and Laboratory Medicine, Groningen University Institute for Drug Exploration , University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Mol Genet Metab. 2007 Dec;92(4):299-307. doi: 10.1016/j.ymgme.2007.07.009. Epub 2007 Sep 7.
Pompe disease is a rare autosomal recessive lysosomal storage disease caused by deficiency of acid-alpha-glucosidase (GAA). This deficiency results in glycogen accumulation in the lysosomes, leading to lysosomal swelling, cellular damage and organ dysfunction. In early-onset patients (the classical infantile form and juvenile form) this glycogen accumulation leads to death. The only therapy clinically available is enzyme replacement therapy, which compensates for the missing enzyme by i.v. administration of recombinant produced enzyme. The development of clinically relevant animal models gained more insight in the disease and allowed evaluation of recombinant enzyme therapy. Several therapies are currently under investigation for Pompe disease, including gene therapy. This review gives an overview of the available knockout mouse models, of the in vitro and in vivo studies performed using recombinant produced enzyme. Furthermore, it describes current therapeutic approaches for Pompe disease as well as experimental therapies like gene correction therapy.
庞贝病是一种罕见的常染色体隐性溶酶体贮积病，由酸性α-葡萄糖苷酶（GAA）缺乏引起。这种缺乏导致糖原在溶酶体中积累，导致溶酶体肿胀、细胞损伤和器官功能障碍。在早发型患者（经典婴儿型和青少年型）中，这种糖原积累会导致死亡。临床上唯一可用的治疗方法是酶替代疗法，即通过静脉注射重组生产的酶来补充缺失的酶。临床相关动物模型的开发使人们对该疾病有了更多了解，并允许对重组酶疗法进行评估。目前正在对庞贝病进行几种治疗方法的研究，包括基因疗法。本综述概述了现有的基因敲除小鼠模型，以及使用重组生产的酶进行的体外和体内研究。此外，它还描述了庞贝病目前的治疗方法以及基因校正疗法等实验性疗法。
