Healthy Living

How an Understanding of Signaling Protein Can Help Treatment with Muscular Dystrophy

How an Understanding of Signaling Protein Can Help Treatment with Muscular Dystrophy

Newer studies have shown that lack of signaling protein would hinder the formation of muscular tissue.This discovery is a milestone for the disease as it could lead to potential treatments in the future.

Muscular dystrophies are a huge group of diseases caused by a genetic mutation. As a result of this genetic mutation, muscles are not able to produce specific proteins essential for their maintenance and growth, thus the muscular tissues in patients slowly break down, causing progressive weakening of muscles. Muscular dystrophies are diseases of young age, and they significantly reduce the lifespan as many of them would ultimately develop respiratory and heart failure. Moreover, the weakening of skeletal muscles in a young age means that there could be years of disability, a poor quality of life, and a high cost of care.

At present, there is no satisfactory treatment for any form of muscular dystrophy and most of the treatment approaches can only slow down the progress of the disease. However, there is lots of research going on in the area, and as researchers continue to uncover the secrets of muscular growth and maintenance, it is entirely possible that some breakthrough would happen in the near future.

Researchers are considering many approaches for muscular repair, from gene editing to testing certain drugs that could help regrow damaged muscles.

Identification of new signal protein in muscle formation

Muscles are very dynamic in the way that they have a great ability to repair and grow. During the physical exertion, muscular fibers are often torn apart. However, these micro tears are soon fixed. In fact, humans preserve the ability to repair and build muscles throughout their whole life, although there is a decrease in this capability as someone ages.

The growth or repair of muscles starts from the multiplication of so-called stem cells. These stem cells, as per the need, multiply and differentiate into the so-called myoblasts. Myoblasts are the building blocks of the muscles; you can compare them as bricks in the wall. However, the wall cannot be built solely with the help of bricks. For making massive walls,bricks must be cemented together. Similarly, myoblasts are fused together to form a muscle fiber. Now, researchers starting to understand how this fusion or cementing of myoblasts happen.

Researchers at the University of Louisville studied the muscular cells of neonates and adults and identified that MyD88 was the signaling protein that is required by the human body in sufficient amount for muscles cells (myoblasts) to fuse together. Hence they found that for the building of muscles availability of plenty of myoblasts was not enough, equally important was the MyD88 (the signaling protein).

In one of the experiments, MyD88 gene was deleted,and researchers found that although the myoblasts continued to multiply and differentiate, but they failed to fuse together to form a muscle fiber. On other hand over-expression of MyD88 promoted the fusion of myoblasts after the injury.

This concept of MyD88 and its role in the formation of muscular fibers were also tested in the genetically modified mice. Researchers created a defect in MyD88 gene in the mice, and they saw that although the myoblasts continued to proliferate but mice failed to form the muscular tissue. Whereas after restoring the ability to produce a MyD88, a fusion of myoblasts started, leading to the formation of muscles.

How could this latest discovery help in muscular degenerative conditions?

Researchers believe that MyD88 can play an important role in the muscular repair, it can be used as a standalone treatment or in combination with other therapies to accelerate the revival of damaged muscles cells. It may even work to halt the damage and degeneration of muscles cells in muscular dystrophies and thus to stop the disease process.

Physical therapy is one of the methods that has been proven to be effective in slowing down the muscular dystrophies. Exercise induces the proliferation of myoblasts; however, myoblasts cannot stick together to strengthen the muscles in the absence of MyD88. Hence if science could find the safe way to induce the higher expression of MyD88, it would help to increase the benefit from such physical therapy. MyD88 can work as a powerful and effective anabolic compound to gain the muscular mass.

At present stem cell therapy is among the fastest emerging field in regenerative medicine. It is a technology in which the so-called stem cells or universal germ cells are replicated in the laboratories. Once these stem cells have been created in enough quantity, they can be injected locally into the weak or damaged muscle where these seed cells would boost the muscular strength by getting converted into myoblasts/muscle cells. However, the effect of this therapy is limited due to the failure of newly formed myoblasts to fuse together and form a muscular fiber. Here is where MyD88 can help the most because it would have the potential to improve the efficacy of cell therapy by manifold.

In conclusion, we can say that numerous studies have shown that MyD88 is essential for the fusion of myoblasts and the formation of muscular tissues. It has been demonstrated to be effective in improving muscular strength in the adults. So, in the future, it could be used either as a standalone therapy or in conjunction with stem cell therapy to treat the muscular dystrophies. But, for this to happen, there needs to be further research and understanding the primary function these myoblasts have in forming muscular structures.

References

  1. Hindi SM, Shin J, Gallot YS, et al. MyD88 promotes myoblast fusion in a cell-autonomous manner. Nature Communications. 2017;8(1):1624. doi:10.1038/s41467-017-01866-w.
  2. Gilbert SF. Myogenesis: The Development of Muscle. 2000. https://www.ncbi.nlm.nih.gov/books/NBK10006/. Accessed December 17, 2017.
  3. UofL. UofL researchers discover key signaling protein for muscle growth — School of Medicine University of Louisville. http://louisville.edu/medicine/news/uofl-researchers-discover-key-signaling-protein-for-muscle-growth. Published November 20, 2017. Accessed December 17, 2017.