Duchenne muscular dystrophy is a genetic disease that affects one of every 3,500 newborn males. Because the DMD gene is located on the X chromosome, loss-of-function mutations that cause Duchenne muscular dystrophy (DMD) tend to occur in males.
Muscular dystrophy or MS affects skeletal muscles and causes muscle weakness and muscle loss, and unfortunately, the disease often progresses to a state were the muscles are so weak and damaged that even the diaphragm, which is a voluntary muscle, becomes nonfunctional, and the patients dies from an inability to breath.
Recently, Michael Rudnicki, a MS researcher from the Ottawa Hospital Research Institute in Canada, has led a research team that discovered that injections of a protein called “WNT7a” into muscles can increase the size and strength of muscles in MS mice.
Rudnicki is the director of the Regenerative Medicine Program at Ottawa Hospital Research Institute (OHRI), Canada. The results of this work were published on the Nov. 26, 2012, in the Proceedings of the National Academy of Sciences (PNAS).
For these experiments, Rudnicki collaborated with a San Diego-based biotechnology firm known as Fate Therapeutics. Fate Therapeutics specializes in developing pharmaceuticals that are based on stem cell biology, and Rudnicki is one of the founders of this company. Rudnicki hopes to begin a clinical trial of WNT7a for DMD in the near future.
In 2009, Rudnicki and co-workers showed that WNT7a protein is able to stimulate muscle repair by increasing the available supply of a population of muscle stem cells known as “muscle satellite cells.” Muscle satellite cells are located near muscle fibers but they are dormant until they are needed for muscle repair or muscle fiber regeneration. When the muscle is stressed or damaged, the satellite cells increase in number (proliferate) and mature (differentiate).
These newly published findings build on these earlier results. Once injected into the muscles of mice afflicted with DMD, the WNT7a-injected muscles showed significant increases in fiber strength and size. However, Rudnicki and others also found that WNT7a stimulated a two-fold increase in the number of satellite cells in the injected mouse muscles.
Rudnicki was worried that WNT7a was pushing satellite cells to differentiate prematurely, which was disconcerting because such premature differentiation would deplete the muscle satellite population. However, no evidence of premature differentiation was observed. Additionally, WNT7a-injected mouse muscles showed far less contraction-related injury, suggesting that WNT7a has a kind of protective effect on the muscle.
Even though these experiments were done in a mouse model of DMD, would WNT7a also work in a similar fashion in human muscles? To answer this questions, Rudnicki and his colleagues analyzed human muscle tissue from healthy male donors that had been treated with WNT7a. The results showed that the effects of this protein in skeletal muscle are the same in humans as in mice.
To summarize from their own paper: “Our experiments provide compelling evidence that WNT7a treatment counteracts the significant hallmarks of DMD, including muscle weakness, making WNT7a a promising candidate for development as an ameliorative treatment for DMD.”
The remarkable conclusion is that increasing muscle strength by injecting WNT7a into specific, vital muscle groups, such as those involved in breathing, should be considered as a therapeutic approach for this debilitating disease.