Researchers reverse key symptom of muscular dystrophy

November 15, 2007

Researchers at the University of Rochester Medical Center have identified a compound that eliminates myotonia – a symptom of muscular dystrophy – in mice. The study was published online today in the Journal of Clinical Investigation.

Rochester scientists were able to design a synthetic RNA-based molecule that, when injected into mice with myotonic dystrophy, restored a critical cellular mechanism, or pathway, that controls electrical activity in muscles. In people with the disease, this function is essentially disabled and muscle cells cannot relax properly. The researchers found that once this pathway was re-established, normal muscle function returned.

“The significance of this work is the proof of concept that a fundamental aspect of this genetic disease can be reversed even after it is very well established,” said Charles Thornton, M.D., co-director of the URMC Neuromuscular Disease Center and senior author of the study. “It encourages us to believe that other parts of the disease could be reversible as well.”

Myotonic dystrophy – the most common form of muscular dystrophy in adults – is characterized by progressive muscle wasting and weakness, particularly in the lower legs, hands, neck, and face. People with myotonic dystrophy have prolonged muscle tensing (myotonia) and are not able to relax certain muscles after use. The condition is particularly severe in the hand muscles and can cause a person’s grip to lock, making it difficult to perform rapid, repeated movements. Consequently, myotonia significantly interferes with a person’s ability to work and function. Myotonia is also one of the earliest signs of myotonic dystrophy and is the symptom by which physicians typically recognize the disease.

Five years ago, Thornton and his colleagues in Rochester helped to unravel the genetic flaw that causes the disease by showing that messenger RNA (mRNA) – responsible for transmitting genetic information out of the nucleus and into the main part of the cell where instructions from the molecular blueprint get carried out – is responsible for the symptoms of the disease. In individuals with myotonic dystrophy, a faulty genetic “stutter” results in the over-production of a certain type of mRNA that, in turn, interferes with other important cellular functions including muscle control.

The regulation of muscle activity and relaxation is basically electrical and is governed by the movement of small charged particles into and out of muscle cells in a very controlled manner. This electrical flow goes through very specific pathways, including one called the chloride channel. In individuals with myotonic dystrophy, the chloride channel is essentially disabled, causing electrical signals in muscles stay “on” for too long, resulting in unstable muscle control – like when someone grasps another’s hand and can’t let go.

The Rochester team, working with the biotechnology company Gene Tools, created a synthetic RNA-based compound that restores the proper genetic instructions for building the chloride channel. When this compound, called a morpholino, was injected into the muscle cells of a set of mice with myotonic dystrophy, the chloride channel was restored and the myotonia all but disappeared and did not return for several weeks.

“This material is incredibly stable in the cells once we get it inside the muscle,” said URMC neurologist Thurman Wheeler, M.D., lead author of the study. “And the effects are surprisingly prolonged, which makes it potentially more attractive as a treatment.”

The Rochester team cautions that more work needs to be done before this new approach can be tested in people. First and foremost, a better method for delivering the compound throughout the body needs to be developed. However, researchers are encouraged by the results and believe that it could ultimately be a step toward a breakthrough treatment for the disease.

“This work should provide hope and encouragement to people with myotonic dystrophy and their families,” said Thornton. “This is a progressive and debilitating condition, but there are early indications that effective treatments are possible. To see a problem like myotonia disappear after it has been present for a long time is certainly a hopeful sign. As we move forward, we should not be content to keep this condition from getting worse. We should set our set our sights on making it better”

Source: University of Rochester

Explore further: Researchers reveal abnormal myokine signaling in congenital myotonic dystrophy

Related Stories

Researchers reveal abnormal myokine signaling in congenital myotonic dystrophy

December 12, 2017
Myotonic dystrophy (DM) is the most common form of genetic muscular dystrophy that begins in adulthood. DM is characterized by progressive muscle wasting and weakness. People with this disorder often have prolonged muscle ...

Study uncovers roles of proteins essential for mouse muscle function; potential link to myotonic dystrophy

November 16, 2016
Myotonic dystrophy, the second most common cause of muscular dystrophy, and numerous other muscle disorders affect tens of thousands of individuals in the U.S.. Paving the way toward a better understanding of these conditions, ...

Potential treatment for most common form of muscular dystrophy

March 18, 2015
A doctor who was one of the discoverers of the gene responsible for myotonic muscular dystrophy has now identified a drug that could slow the progression of muscle damage and muscle dysfunction associated with the disease ...

Recent findings hold new implications for the pathogenesis of myotonic dystrophy

September 12, 2012
An important breakthrough could help in the fight against myotonic dystrophy. The discovery, recently published in the prestigious scientific journal Cell, results from an international collaboration between researchers at ...

Study identifies potential drug targets for muscular dystrophy treatments

January 9, 2017
Myotonic dystrophy type I (MD1) is a common form of muscular dystrophy associated with muscle wasting, weakness, and myotonia. These symptoms are linked to the accumulation of toxic gene transcripts in muscle cells that result ...

A step forward toward muscular dystrophy treatment: 'Antisense' compound rids muscle cells of toxic RNA

August 1, 2012
Scientists have reversed symptoms of myotonic muscular dystrophy in mice by eliminating a buildup of toxic RNA in muscle cells. The work, carried out by scientists at the University of Rochester Medical Center, Isis Pharmaceuticals ...

Recommended for you

Fabric imbued with optical fibers helps fight skin diseases

February 23, 2018
A team of researchers with Texinov Medical Textiles in France has announced that their PHOS-ISTOS system, called the Fluxmedicare, is on track to be made commercially available later this year. The system consists of a piece ...

Low-calorie diet enhances intestinal regeneration after injury

February 22, 2018
Dramatic calorie restriction, diets reduced by 40 percent of a normal calorie total, have long been known to extend health span, the duration of disease-free aging, in animal studies, and even to extend life span in most ...

Artificial intelligence quickly and accurately diagnoses eye diseases and pneumonia

February 22, 2018
Using artificial intelligence and machine learning techniques, researchers at Shiley Eye Institute at UC San Diego Health and University of California San Diego School of Medicine, with colleagues in China, Germany and Texas, ...

Gut microbes protect against sepsis—mouse study

February 22, 2018
Sepsis occurs when the body's response to the spread of bacteria or toxins to the bloodstream damages tissues and organs. The fight against sepsis could get a helping hand from a surprising source: gut bacteria. Researchers ...

Breakthrough could lead to better drugs to tackle diabetes and obesity

February 22, 2018
Breakthrough research at Monash University has shown how different areas of major diabetes and obesity drug targets can be 'activated', guiding future drug development and better treatment of diseases.

Fertility breakthrough: New research could extend egg health with age

February 22, 2018
Women have been told for years that if they don't have children before their mid-30s, they may not be able to. But a new study from Princeton University's Coleen Murphy has identified a drug that extends egg viability in ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.