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Myositis
Published in Jason Liebowitz, Philip Seo, David Hellmann, Michael Zeide, Clinical Innovation in Rheumatology, 2023
Bimagrumab is a monoclonal antibody against type 2 activin receptors which stimulates protein synthesis, muscle growth, and strength. Despite the hypothesis that bimagrumab would promote muscle growth that could outpace muscle loss in IBM, a large, randomized, double-blind phase 2b trial of this medication failed to show efficacy in IBM.128, 129
Peripheral muscles
Published in Claudio F. Donner, Nicolino Ambrosino, Roger S. Goldstein, Pulmonary Rehabilitation, 2020
Luis Puente-Maestu, François Maltais, André Nyberg, Didier Saey
As we are gaining a better understanding of the molecular mechanisms involved in the development of limb muscle dysfunction in COPD (2) and other chronic diseases, it is possible that novel molecules specifically targeting molecular pathways that are responsible for the loss of muscle mass or function will be developed and offer greater efficacy than anabolic drugs that have been tested so far. A promising illustration of this is a recent pilot study in which bimagrumab, a human monoclonal antibody that blocks activin II receptors and its downstream pathway that negatively regulates muscle mass, has been evaluated in patients with COPD (122). The study reported evidence of muscle growth with the monoclonal antibody, but unfortunately, this did not translate into meaningful improvement in muscle function. In this study, the anabolic pharmacological stimuli were provided alone, without any exercise intervention. The existing literature support the notion that the future of anabolic therapies in COPD lies in their concomitant association with exercise training to optimize the benefits and allow them to translate at the clinical and functional levels (111).
Emerging therapeutic targets for osteoporosis
Published in Expert Opinion on Therapeutic Targets, 2020
Luigi Gennari, Daniela Merlotti, Alberto Falchetti, Cristina Eller Vainicher, Roberta Cosso, Iacopo Chiodini
Thus, targeting muscle-fat-bone communication axis could become a potential therapeutic strategy, as fat mass, sarcopenia, and falls have a relevant role on the occurrence of fragility fractures. In this respect, inhibitors of the activin receptor signaling pathway do not only have a direct and positive effect on bone remodeling but also demonstrated to increase muscle mass, becoming potential therapeutics for both osteoporosis and sarcopenia [118,119]. In example, bimagrumab is a recently developed human monoclonal antibody against activin type II receptors, exerting an anabolic action on skeletal muscle by blocking the binding of myostatin and other negative regulators of muscle growth. This compound is actually under evaluation for muscle wasting and associated functional loss in patients with hip fracture and sarcopenia, as well as in obesity and type 2 diabetes. Available results from RCTs indicated that bimagrumab treatment safely increased muscle mass and strength in healthy men following 2 weeks of disuse atrophy as well as in older adults with sarcopenia, and improved mobility in those with slow walking speed [120,121]. A larger phase 2 trial aimed at assessing the efficacy of bimagrumab in patients with muscle wasting after hip fracture surgery has been recently completed, the results of which are not yet publicly available. Moreover, the evidence is also accumulating that myokines other than myostatin (e.g. irisin) or adipokines (e.g. leptin or adiponectin) are able to influence bone metabolism, with potential therapeutic implications [122–124]
Combined medical strategies for the management of type 2 diabetes mellitus and obesity in adults
Published in Expert Opinion on Pharmacotherapy, 2021
Mohamad Sirri Tarazi, Samir Touhamy, Beverly G. Tchang, Alpana P. Shukla
Bimagrumab (BYM338) is a monoclonal antibody against myostatin/activin type 2 (ActRII) receptors. Activation of these receptors promote muscle atrophy; bimagrumab blocks their signaling, which promotes an increase in skeletal muscle mass [105]. In a phase II randomized, double-blinded trial, bimagrumab vs. placebo was conducted in 75 adults with overweight/obesity and T2DM with the primary outcome of change from baseline in total body fat mass at 48 weeks as measured by dual energy x-ray absorptiometry. At the end of study, bimagrumab resulted in 3.6% lean mass gain, 20.5% fat mass loss, and 0.76% HbA1c reduction from baseline. The most common adverse events reported were diarrhoea, nausea, and upper respiratory tract infections [106].
An update on pharmacotherapeutic strategies for obesity
Published in Expert Opinion on Pharmacotherapy, 2021
Beverly G. Tchang, Mohamad Sirri Tarazi, Mohini Aras, Alpana P. Shukla
Bimagrumab (BYM338) is a fully humanized monoclonal antibody against activin type 2 receptors. It competes with endogenous activin ligand to promote differentiation of skeletal myoblasts and counteracts the inhibition of differentiation by myostatin or activin A [81]. In a phase II 48-week randomized, double-blinded trial, bimagrumab vs. placebo was investigated in 75 adults with overweight or obesity and T2D for the primary outcome of fat mass loss [82]. Intravenous bimagrumab administered every 4 weeks at 10 mg/kg resulted in a least squares mean fat mass loss of 7.5 kg vs. 0.2 kg with placebo [82]. Secondary outcome of weight loss was 5.90 kg with bimagrumab vs. 0.8 kg with placebo.