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贝马鲁单抗:一种针对激活素 II 型受体的人源单克隆抗体,用于治疗肥胖症。

Bimagrumab: an investigational human monoclonal antibody against activin type II receptors for treating obesity.

机构信息

Department of Pharmacology, Kalpana Chawla Government Medical College, Karnal, India.

出版信息

J Basic Clin Physiol Pharmacol. 2024 Oct 10;35(6):325-334. doi: 10.1515/jbcpp-2024-0065. eCollection 2024 Nov 1.

DOI:10.1515/jbcpp-2024-0065
PMID:39385353
Abstract

Bimagrumab is a human monoclonal antibody that prevents activin type II receptors (ActRII) from functioning. This antibody has a higher affinity for muscle activin-2 receptors than natural ligands such as activin and myostatin, which act as negative muscle growth regulators. Blocking the activin receptor with bimagrumab could be a new pharmaceutical approach for managing patients with obesity and type 2 diabetes mellitus (T2DM). Bimagrumab has anabolic effects on skeletal muscle mass by preventing myostatin binding and other negative muscle growth regulators. Preclinical animal models have also shown that ActRII blockade promotes actions beyond skeletal muscle, including effects on brown adipose tissue (BAT) differentiation and activity. In a phase 2 randomized clinical trial, ActRII blockade with bimagrumab led to significant loss of total body fat mass (FM), lean mass (LM) gain, and metabolic improvements over 48 weeks in overweight or obese patients with type 2 diabetes. The trial involved [number of participants], and the results showed [specific findings]. Currently, Bimagrumab is being evaluated for its potential to treat muscle wasting, functional loss in hip fractures and sarcopenia, as well as obesity. However, it is essential to note that Bimagrumab also blocks the effects of other ActRII ligands, which play a role in the neurohormonal axes, pituitary, gonads, and adrenal glands. These observations suggest that bimagrumab might represent a new approach for treating patients with obesity and related metabolic disturbances.

摘要

比马鲁单抗是一种人源化单克隆抗体,可阻止激活素型 II 受体(ActRII)发挥作用。与作为负性肌肉生长调节剂的天然配体(如激活素和肌肉生长抑制素)相比,该抗体对肌肉激活素-2 受体具有更高的亲和力。用比马鲁单抗阻断激活素受体可能是治疗肥胖和 2 型糖尿病(T2DM)患者的一种新的药物治疗方法。比马鲁单抗通过阻止肌肉生长抑制素结合和其他负性肌肉生长调节剂,对骨骼肌质量具有合成代谢作用。临床前动物模型还表明,ActRII 阻断除了对骨骼肌有作用外,还能促进棕色脂肪组织(BAT)分化和活性等作用。在一项 2 期随机临床试验中,在超重或肥胖的 2 型糖尿病患者中,比马鲁单抗的 ActRII 阻断导致总体脂肪量(FM)显著减少,48 周内瘦体重(LM)增加,代谢改善。该试验涉及[参与者数量],结果显示[具体发现]。目前,比马鲁单抗正在评估其治疗肌肉减少症、髋部骨折和肌肉减少症的功能丧失以及肥胖的潜力。然而,必须注意的是,比马鲁单抗也会阻断其他 ActRII 配体的作用,这些配体在神经激素轴、垂体、性腺和肾上腺中发挥作用。这些观察结果表明,比马鲁单抗可能代表一种治疗肥胖和相关代谢紊乱患者的新方法。

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Bimagrumab: an investigational human monoclonal antibody against activin type II receptors for treating obesity.贝马鲁单抗:一种针对激活素 II 型受体的人源单克隆抗体,用于治疗肥胖症。
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Antibody blockade of activin type II receptors preserves skeletal muscle mass and enhances fat loss during GLP-1 receptor agonism.抗体阻断激活素 II 型受体可在 GLP-1 受体激动剂作用下保留骨骼肌质量并促进脂肪丢失。
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Effects of bimagrumab, an activin receptor type II inhibitor, on pituitary neurohormonal axes.双羟萘酸贝那鲁肽对垂体神经激素轴的影响。
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Effect of Bimagrumab vs Placebo on Body Fat Mass Among Adults With Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial.贝马鲁单抗对比安慰剂对 2 型糖尿病合并肥胖成人患者体脂量的影响:一项 2 期随机临床试验。
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Blockade of activin type II receptors with a dual anti-ActRIIA/IIB antibody is critical to promote maximal skeletal muscle hypertrophy.用双重抗 ActRIIA/IIB 抗体阻断激活素 II 型受体对于促进最大的骨骼肌肥大至关重要。
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An antibody blocking activin type II receptors induces strong skeletal muscle hypertrophy and protects from atrophy.一种阻断激活素 II 型受体的抗体可诱导强烈的骨骼肌肥大并防止萎缩。
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Activin Type II Receptor Blockade for Treatment of Muscle Depletion in Chronic Obstructive Pulmonary Disease. A Randomized Trial.抑素Ⅱ型受体阻断剂治疗慢性阻塞性肺疾病肌肉消耗:一项随机试验。
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Treatment of sporadic inclusion body myositis with bimagrumab.采用比马鲁单抗治疗散发性包涵体肌炎。
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ActRII blockade protects mice from cancer cachexia and prolongs survival in the presence of anti-cancer treatments.激活素受体II阻断可保护小鼠免受癌症恶病质的影响,并在进行抗癌治疗时延长其生存期。
Skelet Muscle. 2016 Jul 26;6:26. doi: 10.1186/s13395-016-0098-2. eCollection 2016.
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Safety and pharmacokinetics of bimagrumab in healthy older and obese adults with body composition changes in the older cohort.在老年队列中,具有身体成分变化的健康老年和肥胖成年人中,bimagrumab 的安全性和药代动力学。
J Cachexia Sarcopenia Muscle. 2020 Dec;11(6):1525-1534. doi: 10.1002/jcsm.12639. Epub 2020 Dec 2.

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