Richmond.com
Wednesday, May 30, 2007

Barely two months ago, the Stone brothers, Nicholas, 9, and Elliott, 7, received a devastating diagnosis: myotonic muscular dystrophy.

MMD, the most common form of adult muscular dystrophy, is a genetic disease that causes progressive wasting of the muscles of the face, neck, hands and feet and of the organs, including heart, lungs, digestive system and brain. There is no treatment or cure – yet....

DNRonline.com
December 21, 2007

HARRISONBURG - A local businessman has formed a foundation in the hope of partnering with SRI International to find a cure for myotonic muscular dystrophy.

Giles Stone, owner of Mini-Stor-It Self Storage in Harrisonburg, started the Myotonic Muscular Dystrophy Foundation with his son, Todd Stone, after finding out his two grandsons have MMD. No cure exists for the disorder...

Children’s Hospital presents two Spirit of Advocacy Awards each year to recognize the efforts of those advocating for the health care needs of their own child, or the broader needs of children in the community. The first award is presented to a family or family member of a Children’s Hospital patient. The second award recognizes a community partner or professional for using their professional knowledge and resources...

CHARLOTTESVILLE, VA (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.

In this current study, Dr. Mahadevan and his colleagues built upon their groundbreaking research from 2006 which showed that toxic RNA causes DM1 and that getting rid of it actually reversed the disease process. Their latest findings demonstrate a new effect of RNA toxicity and how this may cause cardiac conduction abnormalities.

Entitled, RNA Toxicity in Myotonic Muscular Dystrophy Induces NKX2-5 Expression, the study appears in the December 16, 2007 online edition of Nature Genetics.

HARRISONBURG - Donna and Giles Stone discovered last year that their two grandsons have Myotonic Muscular Dystrophy, a disease that leads to deterioration of muscle and internal organs.....