Fukuda Tokiko, Roberts Ashley, Plotz Paul H, Raben Nina
Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Clinical Center, Bethesda, MD 20892, USA.
Curr Neurol Neurosci Rep. 2007 Jan;7(1):71-7. doi: 10.1007/s11910-007-0024-4.
The development and recent approval of recombinant acid alpha-glucosidase for enzyme replacement therapy have been major milestones in Pompe disease research. Acid alpha-glucosidase is the enzyme responsible for degradation of glycogen polymers to glucose in the acidic milieu of the lysosomes. Cardiac and skeletal muscles are the two major tissues affected by the accumulation of glycogen within the lysosomes. Both cardiomyopathy and skeletal muscle myopathy are observed in patients with complete enzyme deficiency; this form of the disease is fatal within the first year of life. Skeletal muscle myopathy eventually leading to respiratory insufficiency is the predominant manifestation of partial enzyme deficiency. The recombinant enzyme alglucosidase alfa is the first drug ever approved for this devastating disorder. This review discusses the benefits and the shortcomings of the new therapy.
重组酸性α-葡萄糖苷酶用于酶替代疗法的研发及近期获批是庞贝病研究中的重大里程碑。酸性α-葡萄糖苷酶是负责在溶酶体的酸性环境中将糖原聚合物降解为葡萄糖的酶。心脏和骨骼肌是受溶酶体内糖原积累影响的两个主要组织。完全酶缺乏的患者会出现心肌病和骨骼肌肌病;这种疾病形式在生命的第一年就会致命。部分酶缺乏的主要表现是骨骼肌肌病最终导致呼吸功能不全。重组酶阿糖苷酶α是首个获批用于治疗这种毁灭性疾病的药物。本综述讨论了这种新疗法的益处和缺点。