Bimagrumab is a monoclonal antibody targeting αActRIIA and αActRIIB. These receptors are involved in the inhibition of muscle growth via the activity of myostatin; circulating myostatin binds to αActRIIB. Various means of preventing this from happening produce sizable muscle growth in a variety of animal species. Most of the examples involve mutation of the myostatin gene, but a few of the other approaches have made it into clinical trials, including antibodies to reduce circulating myostatin levels and gene therapies to increase circulating levels of follistatin, a protein that blocks the activity of myostatin. The point of all of this is to find a viable approach to produce muscle growth without the need for exercise, and turn back the loss of muscle mass and strength that occurs with age.
Bimagrumab is currently in clinical trials aimed at obesity, as the present generation of GLP-1 receptor agonist drugs used for weight loss produce significant loss of muscle mass alongside loss of fat mass. Drugs that might counteract that undesirable loss of muscle mass are much sought after. In today's open access paper, researchers demonstrate that bimagrumab treatment is quite effective at increasing muscle mass and bone mineral density in mice. This increase in bone mineral density is also a feature of other approaches centered around myostatin, though not so often reported or the focus of research aimed at muscle tissue.
Anti-Activin Receptor Type IIA and Type IIB antibody (αActRIIA/IIB ab) is a recently developed drug class that targets the activin receptor signalling pathway. Inhibition of receptor ligands (activins, myostatin, growth differentiation factor 11, etc.) can lead to skeletal muscle hypertrophy and bone formation. Despite the αActRIIA/IIB ab, bimagrumab, having progressed to clinical trials, two crucial questions about αActRIIA/IIB ab therapy remain: Does αActRIIA/IIB ab influence bone metabolism and bone strength similarly to its generic classmates (activin receptor-based ligand traps)? Therefore, the aim of the present study was to investigate the therapeutic potential of αActRIIA/IIB ab in a mouse model of concurrent sarcopenia and osteopenia and to investigate the effect on bonein more detail.
In C57BL/6JRj mice, combined sarcopenia and osteopenia were induced locally by injecting botulinum toxin A into the right hindlimb, resulting in acute muscle paresis. Immediately after immobilization, mice received twice-weekly intraperitoneal injections with αActRIIA/IIB ab (10 mg/kg) for 21 days, after which they were sacrificed. Muscle mass, skeletal muscle fibre size and Smad2 expression were analysed in the rectus femoris and gastrocnemius muscles. Bone mass and bone microstructure were analysed in the trabecular bone and cortical bone.
αActRIIA/IIB ab caused a large increase in muscle mass in both healthy (+21%) and immobilized (sarcopenic and osteopenic) (+12%) mice. Furthermore, αActRIIA/IIB ab increased trabecular bone (bone volume fraction) for both healthy (+65%) and immobilized (+44%) mice. For cortical bone, αActRIIA/IIB ab caused a small, but significant, increase in bone area (+6%) for immobilized mice, but not for healthy mice. These results suggest a potential in the treatment of concurrent osteopenia and sarcopenia.
View the full article at FightAging
