Rooks D, Swan T, Goswami B et al.
JAMA Network
Link to Pubmed / Journal
Published October 19, 2020
Frailty.net review by Gérard Bozet, MD
Posted November 5, 2020
Sarcopenia is an important health concern in elderly adults because it is associated with adverse outcomes such as falls, disability, and mortality. A previous study showed that frailty can accelerate skeletal muscle loss. Sarcopenia will thus become more of a problem in the near future with the increase in number of elderly people, especially frail or oldest-old adults. Considering the clinical significance of sarcopenia in older adults and the lack of effective treatment options, these promising results indicate that there is hope for older adults with this problem.
Recently, international treatment guidelines for sarcopenia recommended an improved nutritional status, habitual physical activity, and exercise as first-line therapy, although these lifestyle behaviours may be difficult. Adding to the evolving evidence on the effectiveness of adopting improved diet and exercise to improve physical function in later life, there is a surge in the evaluation of new and repurposed pharmacotherapies as potential treatments.
Advances in understanding of the biology associated with ageing, muscle wasting and sarcopenia provide potential targets for drug discovery and are being pursued by the pharmaceutical and biotech industries and academia.
One novel approach targets the myostatin/activin type II receptor (ActRII) pathway to induce the systemic hypertrophy of skeletal muscles, with the expectation of increased muscle strength and improved functional capability.
Bimagrumab is a human monoclonal antibody that binds to type II activin receptors and prevents the binding of its ligands (e.g., myostatin, activin A). These ligands normally act as inhibitors of muscle growth and protein anabolism; bimagrumab lifts this inhibition and can increase muscle mass in young and older adults.
In this 28-week, double-blind, placebo-controlled, parallel-arm, multicentre, phase II randomized clinical trial, participants were provided with a personalised exercise program and recording diary, diet analysis and counselling, an oral nutritional supplement and vitamin D throughout the study period. The top dose of intravenous bimagrumab, 700 mg every 4 weeks, was chosen to maximise potential improvement. The study presents data from all participants randomized to receive bimagrumab 700 mg or placebo for 24 weeks. The primary outcome was the change in Short Physical Performance Battery (SPPB) score after 24 weeks of treatment. Secondary outcomes included 6-minute walk distance, usual gait speed, handgrip strength, lean body mass, fat body mass, and standard safety parameters.
This trial found no significant difference between participants treated with bimagrumab vs placebo among older adults with sarcopenia who had 6 months of adequate nutrition and light exercise, with physical function improving in both groups. Bimagrumab treatment was safe, well-tolerated and increased lean body mass.