Researchers closing in on a medicine against muscle loss
A medicine against the loss of muscle mass in people who are ill and elderly – these are the perspectives in a new research result which has just been published in the journal Science.
When encountered with illness, injury or aging, your muscle mass diminishes and there is currently no medicine to prevent this. But researches from USA and Denmark have just published a study carried out in mice which introduces a method for regulating the activity of muscle stem cells and in this way potentially preventing muscle loss.
This is according to Assistant Professor Jean Farup from the Department of Biomedicine at Aarhus University. He is co-author of the study which has today been published in the journal Science.
“In the longer term, we hope to be able to treat people with reduced muscle mass using a similar treatment strategy as we’ve applied in the research project,” he explains. He emphasises that both aging and diseases such as heart failure, cancer, diabetes and neurological disorders, are strongly associated with the loss of muscle mass, which is again associated with other complications and death. A medicine that can hinder the loss of muscle mass will therefore be more than welcome at a time when life expectancy is increasing – as are the number of associated diseases.
“Of course, there’s still a way to go from mouse to human, but we’ve utilised a type of treatment in the study which is already used on some genetic muscle diseases. The medicine turned out to increase the activity of skeletal muscle stem cells in laboratory mice, and the medicine may thus potentially also counteract the loss of muscle mass. This needs to be tested but all things being equal, the test process will be somewhat quicker when a medicine is already being used by some patient groups," says Jean Farup.
Challenging a dogma
In the study the researchers identified how a particular protein in the stem cells called Pax3 appears to play a major and previously unknown role in the regulation of the skeletal muscle stem cells. A simplified explanation is that too little Pax3 reduce the activity of the muscle stem cells, which in turn leads to the skeletal muscles shrinking and becoming less functional.
”Among people working in the field, the research result represents an important challenge to the dogma that muscle stem cells are inactive under normal conditions,” explains Jean Farup.
“The basic assumption has been that the muscle stem cells first become active when the muscles are damaged by injury or over-training. In contrast, we demonstrate that some muscle stem cells are always in action – and this is also true in ‘peacetime’—which is new and important knowledge about the function of stem cells,” he explains.
Mechanism first followed by medical testing
The researchers began by methodologically mapping the central mechanisms in a study carried out on mice. To do this, the research group examined the activity of stem cells in the muscles by analysing the number of stem cells containing newly-formed DNA. This made it possible for the researchers to show that some muscle stem cells are active in dormant muscles and that Pax3 is a major regulator of this activity. The researchers subsequently found that the skeletal muscles of the mice became smaller and showed impaired functioning when they removed Pax3 – although this obviously does not prove that Pax3 prevents loss of muscle mass.
"The first doesn’t in itself guarantee the second, but it’s likely that this the case," explains Jean Farup. The mechanism study was then followed by the medical testing with the provisionally positive results.
The research group points to one of the strengths of the study; that the muscle stem cells were studied under so-called normal conditions, and not – as in many other stem cell studies – after severe muscle damage such as e.g. having chemicals injected into the muscles. According to Jean Farup, this makes the correlation with humans more direct.
"It’s also not insignificant that both the mechanism mapping and the medical testing have been tested in live animals rather than in a petri dish," he adds.
Jean Farup has been employed as a postdoc while working on the research project at Stanford University together with Professor Thomas Rando, who is the study’s last author and is also affiliated with both Aarhus University and the Steno Diabetes Center Aarhus as an Honorary Skou Professor.
Facts: Loss of muscle mass in elderly and ill people
Loss of muscle mass and muscle strength is a problem for almost all elderly and ill people. The degree of muscle loss partly depends on how well they take care of their body. The consequences are a significant reduction in the ability to perform everyday functions, a reduced ability to survive critical illness and an increased risk of developing a number of complications. Deterioration and loss of muscle mass leads to:
- A reduced ability to perform everyday functions, a slow and uncertain gait and problems climbing stairs
- Increased risk of falls and a general increase in fragility and risk of fractures
- Reduced survival in connection with critical illness such as cancer
- Increased risk of developing other diseases such as type 2 diabetes
The research results – more information
- The research methods are in vivo and in vitro animal studies.
- The most important collaborative partner is Professor Thomas A. Rando, MD, PhD, Stanford University.
- Jean Farup has received external funding from the Lundbeck Foundation and the Independent Research Fund Denmark.
- Direct link to the abstract of the scientific article on which the media coverage is based:
https://science.sciencemag.org/content/366/6466/734
Contact
Assistant Professor Jean Farup
Aarhus University, Department of Biomedicine
Mobil: (+45) 2292 7972
Email: jean@biomed.au.dk