Unboxing the Lab: Researchers Restore Muscle Lost to Aging

[Financial News] A joint research team led by Gyu-Un Bae of the College of Pharmacy at Sookmyung Women's University and Jong-Sun Kang of the College of Medicine at Sungkyunkwan University confirmed that a decline in the Cdon protein is a key feature of the process through which muscles deteriorate with age. The team also identified a compound that restores Cdon levels, suggesting the possibility of improving the mass and function of muscles weakened by aging.
The findings are significant because they identify a new therapeutic target for overcoming age-related sarcopenia, for which fundamental treatments remain limited. Animuscure, a biotech venture founded by the researchers, is conducting a Phase 2 clinical trial of the development candidate AMC6156 in patients. The trial will assess the appropriate dosage and safety, while analyzing whether muscle mass, strength, and physical function actually recover.
The study also points to potential future applications. Researchers are considering developing AMC6156 as a combination therapy to offset muscle loss that may occur during GLP-1-class obesity treatment, as well as a treatment for rare diseases affecting the connection between nerves and muscles. The experimental compound whose mechanism of action and efficacy were confirmed in this study is AMC6156. The paper presents preclinical findings based on human genetic data, cells, and mouse models.

The research team first examined the molecular changes that occur in human muscles as they age. They analyzed skeletal-muscle gene data from 891 people registered in the large-scale human tissue database Genotype-Tissue Expression (GTEx). The results showed that lower Cdon expression was associated with greater activity of genes linked to muscle atrophy. This indicates that reduced Cdon expression is closely associated with muscle aging and a decrease in muscle-fiber size.
Similar differences were also confirmed in actual human muscle cells. When the team compared muscle cells obtained from a 17-year-old man and a 68-year-old man, the amount of Cdon protein was substantially lower in the cells from the 68-year-old.
The researchers also noted that the metabolite cysteine was abnormally elevated in both patients with sarcopenia and aged mice. Cell experiments showed that excessive cysteine accumulation impaired mitochondrial respiration and energy metabolism while increasing oxidative stress. Cdon protein levels also declined under this stressful environment.
The team conducted drug screening to find a way to increase Cdon again. It built an analysis system using the gene-regulatory region of Cdon and screened a library of 2,485 drugs approved by the U.S. Food and Drug Administration (FDA). The screening identified AMC6156 as a compound that induces Cdon expression.

The researchers also identified how AMC6156 restores Cdon. When AMC6156 was applied to muscle cells, the AMP-activated protein kinase (AMPK) signal, which senses and regulates cellular energy metabolism, was activated within five minutes. The response lasted for up to four hours. As AMPK was activated, excessive cysteine accumulation decreased and Cdon protein remained stable. The metabolic function and antioxidant defense system of damaged mitochondria also recovered.
The effects observed in cells were confirmed in animal experiments. Aged mice 16 months old were given AMC6156 daily for 10 weeks. Their muscle mass and grip strength, measured by their ability to grasp objects with their forepaws, improved significantly. Neuromuscular transmission signals, which carry stimuli from nerves to muscles, also improved. Muscle-tissue damage and fibrosis, in which tissue becomes abnormally stiff, were reduced as well.
Among the muscle fibers, the cross-sectional area and related proteins of fast-twitch fibers (type IIB), which generate force rapidly, also improved.
The effects were not limited to muscle. Aged mice treated with AMC6156 showed improved fasting blood-glucose regulation, while the amount of fat accumulated in the liver decreased.
The study is drawing attention because it confirms that reduced Cdon protein is a key feature of muscle aging and proposes a therapeutic strategy for maintaining Cdon through AMPK activation. However, because the paper reports preclinical experimental results, the efficacy and safety of the treatment in human patients remain to be verified through analysis of the ongoing Phase 2 clinical trial of AMC6156.
[email protected] Man-Ki Kim Reporter