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首页> 外文期刊>Journal of Cachexia, Sarcopenia and Muscle >Effect of bimagrumab on thigh muscle volume and composition in men with casting-induced atrophy
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Effect of bimagrumab on thigh muscle volume and composition in men with casting-induced atrophy

机译：Bimagrumab对铸型性萎缩男性大腿肌肉体积和成分的影响

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Abstract Background Patients experiencing disuse atrophy report acute loss of skeletal muscle mass which subsequently leads to loss of strength and physical capacity. In such patients, especially the elderly, complete recovery remains a challenge even with improved nutrition and resistance exercise. This study aimed to explore the clinical potential of bimagrumab, a human monoclonal antibody targeting the activin type II receptor, for the recovery of skeletal muscle volume from disuse atrophy using an experimental model of lower extremity immobilization. Methods In this double-blind, placebo-controlled trial, healthy young men ( n = 24; mean age, 24.1 years) were placed in a full-length cast of one of the lower extremities for 2 weeks to induce disuse atrophy. After cast removal, subjects were randomized to receive a single intravenous (i.v.) dose of either bimagrumab 30 mg/kg ( n = 15) or placebo ( n = 9) and were followed for 12 weeks. Changes in thigh muscle volume (TMV) and inter-muscular adipose tissue (IMAT) and subcutaneous adipose tissue (SCAT) of the thigh, maximum voluntary knee extension strength, and safety were assessed throughout the 12 week study. Results Casting resulted in an average TMV loss of ?￠????4.8% and comparable increases in IMAT and SCAT volumes. Bimagrumab 30 mg/kg i.v. resulted in a rapid increase in TMV at 2 weeks following cast removal and a +5.1% increase above pre-cast levels at 12 weeks. In comparison, TMV returned to pre-cast level at 12 weeks (?￠????0.1%) in the placebo group. The increased adiposity of the casted leg was sustained in the placebo group and decreased substantially in the bimagrumab group at Week 12 (IMAT: ?￠????6.6%, SCAT: ?￠????3.5%). Knee extension strength decreased by ~25% in the casted leg for all subjects and returned to pre-cast levels within 6 weeks after cast removal in both treatment arms. Bimagrumab was well tolerated with no serious or severe adverse events reported during the study. Conclusions A single dose of bimagrumab 30 mg/kg i.v. safely accelerated the recovery of TMV and reversal of accumulated IMAT following 2 weeks in a joint-immobilizing cast.
机译：摘要背景经历了萎缩性萎缩的患者报告骨骼肌质量急剧下降，继而导致力量和体能的丧失。对于这类患者，尤其是老年人，即使改善营养和抵抗运动，要完全康复仍然是一个挑战。这项研究旨在探索bimagrumab（一种针对激活素II型受体的人单克隆抗体）在使用下肢固定实验模型从废用性萎缩中恢复骨骼肌体积方面的临床潜力。方法在这项双盲，安慰剂对照试验中，将健康的年轻男性（n = 24;平均年龄，24.1岁）放在下肢之一的全长石膏中2周，以诱导废用性萎缩。去除石膏后，将受试者随机接受单次静脉（i.v.）剂量的30 mg / kg比格鲁单抗（n = 15）或安慰剂（n = 9），并随访12周。在整个12周的研究中，评估了大腿的肌肉体积（TMV）和肌肉间脂肪组织（IMAT）和皮下脂肪组织（SCAT）的变化，最大自愿膝盖伸展力量和安全性。结果铸造导致平均TMV损失为4.8％，并且IMAT和SCAT量有相当的增加。 Bimagrumab 30 mg / kg静脉注射导致在去除铸件后2周TMV迅速增加，并在12周时比预制水平高出+ 5.1％。相比之下，在安慰剂组中，TMV在第12周时恢复到预制水平（0.1％）。在第12周时，安慰剂组的cast腿肥胖得以维持，而双曲单抗组则显着下降（IMAT：6.6％，SCAT：3.5％）。所有受试者的the腿的伸膝力量下降了约25％，并且在两个治疗组中的cast子切除后6周内恢复到预制水平。在研究期间，Bimagrumab的耐受性良好，没有严重或严重不良事件的报道。结论单剂量bimagrumab 30 mg / kg i.v.在联合固定的石膏模型中放置2周后，可以安全地加速TMV的恢复和IMAT的累积逆转。

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