MYOSTATIN INHIBITOR ACE-031 TREATMENT OF AMBULATORY BOYS WITH DUCHENNE MUSCULAR DYSTROPHY: RESULTS OF A RANDOMIZED, PLACEBO- CONTROLLED CLINICAL TRIAL
MYOSTATIN INHIBITOR ACE-031 TREATMENT OF AMBULATORY BOYS WITH DUCHENNE MUSCULAR DYSTROPHY: RESULTS OF A RANDOMIZED, PLACEBO- CONTROLLED CLINICAL TRIAL
复制标题
DOI：
10.1002/mus.25268
复制
发表时间：
2017-04-01
期刊：
影响因子：
3.4
通讯作者：
Attie, Kenneth M.
中科院分区：
文献类型：
--
作者：
Campbell, Craig;Mcmillan, Hugh J.;Attie, Kenneth M.
ACE- 031是一种Ⅱ B型激活素受体与IgG 1- Fc的融合蛋白，可与肌生长抑制素及相关配体结合。它旨在破坏对肌肉发育的抑制作用，并为杜氏肌营养不良症（DMD）等肌病提供潜在的治疗方法。研究方法：在一项随机、双盲、安慰剂对照、剂量递增的试验中，DMD男孩每2- 4周皮下注射ACE- 031。主要目的是安全性评价。次要目的包括药代动力学和药效学表征。结果：ACE- 031与严重或严重不良事件无关。由于鼻衄和毛细血管扩张的潜在安全性问题，在第二次给药方案后停止研究。观察到ACE- 031组中6分钟步行试验（6 MWT）距离保持不变的趋势，而安慰剂组下降（无统计学显著性），以及瘦体重和骨矿物质密度（BMD）增加和脂肪量减少的趋势。结论：ACE- 031的使用表现出对瘦体重、脂肪量、BMD和6 MWT的药效学效应趋势。非肌肉相关的不良事件导致了中止研究的决定。肌生长抑制素抑制剂是治疗DMD的一种有前途的方法。
Introduction: ACE- 031 is a fusion protein of activin receptor type IIB and IgG1- Fc, which binds myostatin and related ligands. It aims to disrupt the inhibitory effect on muscle development and provide potential therapy for myopathies like Duchenne muscular dystrophy ( DMD). Methods: ACE- 031 was administered subcutaneously every 2- 4 weeks to DMD boys in a randomized, double- blind, placebo- controlled, ascending- dose trial. The primary objective was safety evaluation. Secondary objectives included characterization of pharmacokinetics and pharmacodynamics. Results: ACE- 031 was not associated with serious or severe adverse events. The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. A trend for maintenance of the 6- minute walk test ( 6MWT) distance in the ACE- 031 groups compared with a decline in the placebo group ( not statistically significant) was noted, as was a trend for increased lean body mass and bone mineral density ( BMD) and reduced fat mass. Conclusion: ACE- 031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT. Non- muscle- related adverse events contributed to the decision to discontinue the study. Myostatin inhibition is a promising therapeutic approach for DMD.