muscular dystrophy

The term muscular dystrophy (MD) refers  to a group of disorders in which a genetic abnormality causes muscles responsible for controlling movement to become weak, and muscle mass to be lost. These inherited disorders usually affect voluntary (skeletal) muscles, although weakness can also extend to the muscles that control respiration and swallowing.

Given that the genetic mutations triggering MD interfere with the normal production of certain critical proteins, the body is not able to reverse muscle weakening or loss of mass, so even when the disease progresses slowly, it eventually affects one’s ability to walk in a more or less conducive manner.

Who is affected by muscular dystrophy?

In most cases MD appears in infancy, but it’s not uncommon for symptoms to start manifesting in teens or adults.

Muscle fibres formed in the lab by human mesoangioblasts (image: eurostemcell)

  Muscle fibers formed in the lab by human mesoangioblasts     (image: eurostemcell).

Although the manifestations are similar, their severity varies depending on the age at which the disease occurs. In some, the symptoms are mild and sufferers are able to continue living almost normally, while in others the ailment is extremely disabling and can lead to muscle wasting, loss of the ability to walk, and even death.

There are different kinds of muscular dystrophy, the most common and severe  form being Duchenne muscular dystrophy (DMD) Caused by a genetic flaw or defect, Duchenne MD is more common in males than females [1} and affects about 1 in every 3,500 boys worldwide.

The onset of Duchenne muscular dystrophy occurs between the ages of 2 and 6, and evolves slowly. Muscles becoming weaker year after year, and the spine and limbs becoming progressively deformed. In most cases, children affected by this form of the disease become wheelchair dependent by the age of 12.

People suffering from Duchenne MD often die in their 20s, and those who survive usually experience some degree of cognitive impairment. The shortening of tendons and muscles limits the mobility of sufferers even more, and breathing and heart problems can occur.

Treatments for Duchenne muscular dystrophy

muscular dysrophy

Muscular dystrophy is a genetic disorder where the muscle tissue wastes away and loses function. In the affected muscle (left), the tissue has become disorganized and the concentration of dystrophin (green), an important protein in normal muscle functioning, is greatly reduced. (Image: Wikipedia)

There is currently no known cure for DMD, but there are treatments that help to reduce some of the symptoms and strengthen the patient’s muscles to some degree.

Physiotherapy is commonly used for slowing down the loss of muscle mass and for maintaining flexibility or reducing muscle stiffness. Steroids are also used to slow down muscle wasting, but the severe side effects of steroids often cause more harm than good,  such as bone weakening or cardiovascular problems.

In a healthy organism, damaged muscles repair themselves thanks to a series of cells that include muscle stem cells, called satellite cells. In Duchene muscular dystrophy, the muscles lack dystrophin, the protein needed for maintaining the integrity of  muscle fibers. Without this protein, the burden placed on the body’s naturally occurring muscle stem cells is too intense, rendering the cells unable to repair damaged muscle tissue or to generate new muscle mass to replace wasted mass [6].

For this reason, scar tissue and fat cells take the place of damaged muscle tissue, contributing to muscle weakening and, over time,  cause muscles to lose their functional ability. Would it be possible for the damaged muscle fibers to regain their regenerative ability with help from transplanted stem cells?

Research suggests stem cells could be a potential solution for muscle wasting

multiple dystrophy

(Click on image to enlarge) Considerable efforts are underway to develop drugs and biologics (cell and gene therapy) to address the primary problem in Duchenne—the absence of dystrophin. Restoring dystrophin or replacing dystrophin with replacement protein are considered foundational therapies.

Different strategies involving stem cells for muscular dystrophy may be on the horizon, research suggests. Scientists have been using stem cells isolated from muscle tissue, bone marrow and blood vessels in lab animals to regenerate muscle fibers that are deficient in dystrophin[3] and results are  encouraging.

In 2006, researchers managed to restore mobility in two  afflicted dogs using stem cells isolated from muscle blood vessels [4], and in 2007 scientists managed to treat Duchenne MD in research mice using a combination of genetic correction and stem cells [3]. The latter study showed that it is possible to correct the genetic error in the cells that no longer produce dystrophin protein, and inject corrected cells stimulating the regeneration of muscles.

Researchers at the Harvard Stem Cell Institute obtained similar results, demonstrating that transplanted muscle stem cells can improve function in mice with MD, while replenishing the stem cell population in muscle fibers [5].

Although it’s still too early to say whether stem cells can cure DMD in humans, it’s clear that there are some promising stem-cell-based approaches for Duchenne MD. One solution is to replace the defective stem cells with healthy stem cells, as these may be able to generate working muscle fibers to replace damaged muscle fibers .

A second solution would be to reduce the inflammation that speeds up the loss and weakening of muscles using certain types of stem cells [2]. Combined treatments, such as mixing stem cell therapies with gene therapies are also being tested and may prove successful in the near future.

References:

  1. http://www.mayoclinic.org/diseases-conditions/muscular-dystrophy/basics/definition/con-20021240
  2. http://www.eurostemcell.org/factsheet/muscular-dystrophy-how-could-stem-cells-help
  3. https://www.mda.org/disease/duchenne-muscular-dystrophy/research
  4. http://quest.mda.org/article/scientists-bullish-stem-cells-muscle-repair
  5. http://hsci.harvard.edu/stem-cells-used-treat-muscular-dystrophy-mice
  6. https://med.stanford.edu/news/all-news/2014/12/stem-cells-faulty-in-duchenne-muscular-dystrophy.html