A new drug for muscle aging

© EPFL/iStock
Scientists at EPFL have developed ALT-007, a safe, oral compound that restores muscle mass and function in aging mice, potentially offering a novel treatment for age-related muscle loss and neuromuscular diseases.
As we age, our muscles gradually lose mass and strength, a condition known as sarcopenia. This process can limit mobility, independence, and quality of life for millions of older adults. While lifestyle changes like exercise and nutrition can help, they often aren’t enough to counteract the underlying biological causes of muscle decline. For years, researchers have sought effective treatments, but options have been scarce.
Recent studies from the Auwerx laboratory at EPFL have linked sarcopenia and muscle disorders to the accumulation of ceramides, a type of fat that plays a critical role in cell signaling. These molecules can disrupt protein balance in muscle cells, leading to tissue damage and reduced function. Despite this knowledge, targeting ceramides has been challenging due to the lack of safe and effective drugs.
Now, a team of scientists led by Johan Auwerx has now developed ALT-007, a potent inhibitor of ceramide synthesis. By targeting serine palmitoyltransferase, the key enzyme in ceramide production, ALT-007 effectively reduces harmful ceramide levels. In aging mice, the drug reversed muscle loss and improved physical performance. The compound can pave the way for new treatments to address sarcopenia and related neuromuscular diseases.

ALT-007 was tested in aging mice over a 20-week period. The aged mice, treated through their diet, showed no signs of toxicity, maintaining normal weight and food intake. Further testing confirmed that ALT-007 reduced ceramide levels, particularly harmful very-long-chain ceramides, in muscle tissue. The drug’s effects were further validated using RNA sequencing, revealing improved protein balance and activation of key cellular pathways that support muscle and neuronal health.
Mice treated with ALT-007 exhibited significant gains in muscle mass and strength compared to untreated mice. Tests measuring grip strength, coordination, and endurance showed marked improvements, with some metrics resembling those of much younger mice. Beyond muscle health, ALT-007 also enhanced physical activity levels and energy expenditure, reflecting a broader boost in fitness and vitality.
In addition to these physical benefits, ALT-007 demonstrated its impact on cellular processes. The drug improved protein balance in muscle cells by reducing harmful protein aggregates linked to aging and neuromuscular diseases. Remarkably, ALT-007’s benefits extended to the brain, where it reduced levels of toxic fats implicated in neurological decline.
The implications of ALT-007 are profound. For millions of older adults facing the debilitating effects of sarcopenia, this drug could offer a lifeline. Beyond aging-related muscle loss, ALT-007 holds promise for treating a range of conditions, including neurodegenerative diseases like Alzheimer’s and rare genetic disorders that affect muscle function. Its dual impact on muscle and brain health highlights its potential as a versatile therapy.
Other contributors
Intonation Research Laboratories
EPFL
European Research Council (ERC)
Swiss National Science Foundation (SNSF)
Global Research Laboratory (GRL) National Research Foundation of Korea
Johanne Poisson, Ioanna Daskalaki,VijayPotluri,Jean-David Morel, Sandra Rodriguez-Lopez, Alessia De Masi, Giorgia Benegiamo, Suresh Jain, Tanes Lima, Johan Auwerx. A safe and orally bio-available inhibitor of serine palmitoyltransferase improves age-related sarcopenia. ACS Pharmacology & Translational Science 29 December 2024. DOI: 10.1021/acsptsci.4c00587