For muscle-wasting disorders such as muscular dystrophy, there are currently no treatments to halt progression. But researchers from the Sanford-Burnham Medical Research Institute in La Jolla, CA, say they may have found a way to trigger tissue repair in damaged muscles, which could help treat such conditions.
Image credit: Sanford-Burnham Medical Research Institute
Muscular dystrophy is a group of genetic conditions characterized by progressive muscle weakness. It is caused by defects in the genes that are responsible for protecting the muscle fibers from damage.
The research team, led by Alessandra Sacco, PhD, assistant professor in the Development, Aging and Regeneration Program at Sanford-Burnham, explains that when muscles are subject to damage, satellite cells – muscle stem cells – need to differentiate into mature muscle cells to trigger muscle fiber repair.
In case of future muscle damage, however, these satellite cells need to be replenished. The team says this does not happen in people with muscular dystrophy, as their stocks of satellite cells are drained due to the continuous damage their muscles are subject to.
But in this latest study, published in the journal Nature Medicine, Sacco and his team say they may have identified a way to continuously replenish stocks of satellite cells and trigger repair of damaged muscles.
The process involves repeatedly blocking a protein called signal transducer and activator of transcription 3 (STAT3).
- Muscular dystrophy is more common among males than females
- It is unknown as to how many people in the US have muscular dystrophy, although data from 2007 suggested that 1 in every 5,600-7,700 males aged 5-24 years has Duchenne/Becker muscular dystrophy (DBMD) – the most common forms of the disorder
- In 2007, more than 90% of males aged 15-24 with DBMD were using a wheelchair.
According to the researchers, past studies have shown that STAT3 plays an important role in skeletal muscle. They note that it promotes muscle repair in some cases but interferes with it in others.
To test its effect on muscle repair in the case of muscular dystrophy, the team gave STAT3-inhibiting drugs to mouse models with the disease, as well as mice that had normal muscle weakness due to aging.
They found that the drug triggered replication of satellite cells in both the mouse models of muscular dystrophy and normally aged mice, before differentiating these cells into muscle fibers. After administering the drug once a week for 28 days, the researchers found that the mice demonstrated overall improvement in muscle repair and the muscle fibers had increased in size.
The researchers then tested the STAT3-inhibitor on human muscle cells, which produced similar effects. “We have discovered that by timing the inhibition of STAT3 – like an ‘on/off’ light switch – we can transiently expand the satellite-cell population followed by their differentiation into mature muscle cells,” explains Sacco.
The team says their findings pave the way for new treatment strategies for individuals with muscle-degenerating diseases, as well as those who experience muscle weakness as a result of cancer and aging.
Commenting on these results, Dr. Vittorio Sartorelli, deputy scientific director at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and chief of its Laboratory of Muscle Stem Cells and Gene Regulation, says:
“These findings are very encouraging. Currently, there is no cure to stop or reverse any form of muscle-wasting disorders, only medication and therapy that can slow the process. A treatment approach consisting of cyclic bursts of STAT3 inhibitors could potentially restore muscle mass and function in patients, and this would be a very significant breakthrough.”
Sacco says they now plan to work on extending the muscle cell replication and muscle fiber repair process. In addition, they want to test some of the STAT3 inhibitors used in other clinical trials in the hope that it will bring them closer to human clinical trials.
Earlier this year, Medical News Today reported on a study suggesting Duchenne muscular dystrophy – one of the most common forms of the condition – could be treated with an erectile dysfunction drug.