UVA reports surprising findings related to myotonic muscular dystrophy

Dec 17, 2007

New research from the University of Virginia Health System shows that, in cases of Type 1 myotonic muscular dystrophy (DM1), a well known heart protein does several surprising things. DM1 is the most common form of muscular dystrophy in adults and affects approximately 40,000 adults and children in the U.S.

The protein, NKX2-5, is a biomarker for heart stem cells. It is also very important for the normal development of the heart. “Too little of it causes major cardiac problems including slow and irregular heartbeats,” observes Dr. Mani Mahadevan, a human genetics researcher and Professor of Pathology at UVa who led the study.

The researchers were surprised to find that mice and individuals with DM1 actually overproduce NKX2-5, yet experience the same kind of heart problems associated with too little of it.

Excessive NKX2-5 may explain why as many as 60 to 70 percent of individuals with DM1 develop heart problems which cause their heartbeats to become slow and irregular, often necessitating the need for pacemakers. If these irregular heartbeats are not detected, sudden death can occur.

By using the mouse model of DM1 and mice genetically engineered to produce less NKX2-5, Dr. Mahadevan and his team showed that reducing the excessive levels of NKX2-5 seemed to protect the mice from the heart problems.

Researchers were also surprised to find NKX2-5 in the muscles of mice and individuals with DM1. “Usually, NKX2-5 is found only in the heart of adults,” Dr. Mahadevan notes. “It’s like the muscle is having some kind of ‘identity crisis’ and starting to make proteins that shouldn’t be there normally.”

This discovery could prove beneficial, says Dr. Mahadevan, and lead to development of a simple diagnostic test to follow a patient’s response to potential therapies.

Myotonic muscular dystrophy is recognized as the first example of a disease caused by a toxic RNA. RNAs are intermediary molecules that convey the genetic code in the DNA to the rest of the cell. RNAs are normally “cut and pasted together” by a process called RNA splicing. It is currently thought that the toxic RNA causes DM1 by disrupting normal RNA splicing.

“Much of the research on DM1 is focused on factors that cause RNA splicing defects. Our work may provide explanations for pathogenic effects not accounted for by RNA mis-splicing,” Mahadevan explained.

Source: University of Virginia Health System

Explore further: New urine test could reduce need for blood samples

Related Stories

Architects to hatch Ecocapsule as low-energy house

14 hours ago

Where people call home depends on varied factors, from poverty level to personal philosophy to vanity to community pressure. Ecocapsule appears to be the result of special factors, a team of architects applying ...

California farmers agree to drastically cut water use

18 hours ago

California farmers who hold some of the state's strongest water rights avoided the threat of deep mandatory cuts when the state accepted their proposal to voluntarily reduce consumption by 25 percent amid ...

Apple may deliver ways to rev up the iPad, report says

18 hours ago

MacRumors last month said that the latest numbers from market research firm IDC's Worldwide Quarterly Tablet Tracker revealed Apple stayed on as the largest vendor in a declining tablet market. The iPad ...

Recommended for you

User comments : 0

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.