Key result
Myostatin and activin receptor drugs fail trials due to adverse events or poor functional improvement.
Why the study?
Current treatments for debilitating muscle wasting diseases are relatively ineffective, making therapeutics that disrupt myostatin and activin receptor signaling a promising yet challenging approach.
While drugs targeting myostatin and activin receptor signaling show promise for preventing muscle wasting, clinical translation has been hindered by safety issues and a lack of functional improvement.
Answers are grounded in this paper and cite their sources.
Safety concerns and absent functional gains warrant clinical caution; leaves open refined pathway targeting for muscle preservation.
Muscle wasting disease indications are among the most debilitating and often deadly noncommunicable disease states. As a comorbidity, muscle wasting is associated with different neuromuscular diseases and myopathies, cancer, heart failure, chronic pulmonary and renal diseases, peripheral neuropathies, inflammatory disorders, and, of course, musculoskeletal injuries. Current treatment strategies are relatively ineffective and can at best only limit the rate of muscle degeneration. This includes nutritional supplementation and appetite stimulants as well as immunosuppressants capable of exacerbating muscle loss. Arguably, the most promising treatments in development attempt to disrupt myostatin and activin receptor signaling because these circulating factors are potent inhibitors of muscle growth and regulators of muscle progenitor cell differentiation. Indeed, several studies demonstrated the clinical potential of “inhibiting the inhibitors,” increasing muscle cell protein synthesis, decreasing degradation, enhancing mitochondrial biogenesis, and preserving muscle function. Such changes can prevent muscle wasting in various disease animal models yet many drugs targeting this pathway failed during clinical trials, some from serious treatment-related adverse events and off-target interactions. More often, however, failures resulted from the inability to improve muscle function despite preserving muscle mass. Drugs still in development include antibodies and gene therapeutics, all with different targets and thus, safety, efficacy, and proposed use profiles. Each is unique in design and, if successful, could revolutionize the treatment of both acute and chronic muscle wasting. They could also be used in combination with other developing therapeutics for related muscle pathologies or even metabolic diseases.
No takes yet. Share an insight, caveat, or question.
Rodgers et al. (2021) conducted a review in Muscle wasting diseases. Myostatin and activin receptor attenuating drugs was evaluated. Drugs targeting myostatin and activin receptor signaling aim to treat muscle wasting, but many clinical trials have failed due to adverse events or an inability to improve muscle function.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: