Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa
Effects of enzyme replacement therapy on the cardiomyopathy of Anderson-Fabry disease: a randomised, double-blind, placebo-controlled clinical trial of agalsidase alfa
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DOI：
10.1136/hrt.2006.104026
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发表时间：
2008-02-01
期刊：
影响因子：
5.7
通讯作者：
Mehta, A. B.
中科院分区：
文献类型：
--
作者：
Hughes, D. A.;Elliott, P. M.;Mehta, A. B.
背景：Anderson-Fabry病是一种由溶酶体α -半乳糖苷酶a活性不足引起的x连锁鞘糖脂储存障碍。这种疾病会导致全身体细胞溶酶体中球三烷基神经酰胺（Gb(3)）的进行性积累，最终导致肾、心或脑血管并发症导致的过早死亡。直到最近，这种疾病还没有有效的治疗方法。本研究旨在评估琼脂苷酶替代疗法对安德森-法布里病心脏表现的安全性和有效性。方法：在一项随机、双盲、安慰剂对照的研究中，对15例成年男性安德森-法布里病患者进行了琼脂苷酶治疗对心脏结构和功能的影响。在基线和6个月时测量以下参数：左心室质量、QRS持续时间、心脏组织中Gb(3)水平、尿沉积物和血浆。在6个月的随机试验后，患者被纳入一项为期2年的开放标签扩展研究。结果：与安慰剂相比，琼脂苷酶治疗6个月后，通过MRI测量的左心室质量显著减少（p= 0.041）。经系列经静脉心内膜活检评估，在6个月的酶替代治疗中，心肌Gb(3)含量平均降低了20%，而安慰剂组的心肌Gb(3)含量平均增加了10% （p= 0.42）。结论：琼脂苷酶替代治疗导致安德森-法布里病相关肥厚性心肌病的消退。
Background: Anderson-Fabry disease is an X-linked glycosphingolipid storage disorder caused by deficient activity of the lysosomal enzyme alpha-galactosidase A. This leads to a progressive accumulation of globotriaosylceramide (Gb(3)) in the lysosomes of cells throughout the body that ultimately results in premature death from renal, cardiac or cerebrovascular complications. Until recently, there was no effective therapy available for this disease. The present study was designed to assess the safety and efficacy of enzyme replacement therapy with agalsidase alfa on the cardiac manifestations of Anderson-Fabry disease.Method: The effects of therapy with agalsidase alfa on cardiac structure and function were assessed in a randomised, double-blind, placebo-controlled study of 15 adult male patients with Anderson-Fabry disease. The following parameters were measured at baseline and 6 months: left ventricular mass, QRS duration and levels of Gb(3) in cardiac tissue, urine sediment and plasma. After 6 months of the randomised trial patients were enrolled in a 2- year open-label extension study.Results: Left ventricular mass, as measured by MRI, was significantly reduced following 6 months of treatment with agalsidase alfa compared with placebo (p= 0.041). A mean 20% reduction in myocardial Gb(3) content as assessed by serial transvenous endomyocardial biopsies was demonstrated over the 6 months of enzyme replacement compared to a mean 10% increase in patients receiving placebo (p= 0.42)Conclusion: Enzyme replacement therapy with agalsidase alfa resulted in regression of the hypertrophic cardiomyopathy associated with Anderson-Fabry disease.