MDA RESEARCHERS FIND CLUE
TO EYE AND MUSCLE PROBLEMS IN ADULT DYSTROPHY

TUCSON, Ariz., Dec. 12, 2003 — Investigators at the University of Florida in Gainesville and the University of Rochester (N.Y.) have found that interference with a set of proteins called muscleblind is likely to be a major cause of myotonic muscular dystrophy (MMD), the Muscular Dystrophy Association announced today. MMD is the most common form of muscular dystrophy in adults.

MDA-supported geneticist Maurice Swanson at the University of Florida and MDA-funded neurologist Charles Thornton at the University of Rochester were part of a team that published the muscleblind findings in today’s issue of Science.

The loss of the contributions made by muscleblind proteins, named for their essential role in the maturation of muscles and eyes, is probably responsible for the muscular and ocular abnormalities that are prominent in MMD, the investigators say.

The researchers confirmed previous observations that, in MMD-affected cells, muscleblind protein molecules stick to excess genetic material called RNA (ribonucleic acid) in each cell nucleus. Today’s findings reveal that the RNA-muscleblind clumps keep the muscleblind proteins from performing their cellular duties.

To test the importance of the muscleblind clumping, the researchers bred mice missing one form of muscleblind protein. These mice developed myotonia (difficulty relaxing muscles) and ocular cataracts, both features of MMD in people.

In addition, the muscles of the mice showed cells with abnormally positioned nuclei and split fibers when viewed under the microscope, as well as flaws in proteins related to heart function and to the movement of chloride particles. These are all characteristics of MMD.
The new finding comes on the heels of a discovery by MDA-supported investigator Richard Junghans at Harvard University in Boston that proteins called transcription factors are affected in MMD. Transcription factors are needed to manufacture other cellular proteins. Junghans’ paper was published in the Dec. 4 issue of Science Express.

“Myotonic dystrophy is a complicated puzzle, the pieces of which are finally falling into place,” said Sharon Hesterlee, MDA’s director of research development. “This most recent work not only provides us with a much-needed new mouse model for this disease, but it also may provide a new therapeutic target.”

The muscleblind-deficient mice didn’t display all MMD-related signs and symptoms, investigators say, because only one type of muscleblind protein was missing from the mice. Other factors also may be involved, Swanson said.

Swanson commented, “Our results suggest that restoration of normal levels of functional muscleblind protein might prove to be a useful therapeutic approach for treating both muscle and eye problems associated with MMD.”

MMD, which affects some 38,000 people in the United States, causes muscle weakness, myotonia, premature balding, cataracts, digestive and gynecological abnormalities, heartbeat irregularities, and mild to moderate brain dysfunction.

MDA is a voluntary health agency working to defeat more than 40 neuromuscular diseases, including the MDs, through programs of worldwide research, comprehensive services, and far-reaching professional and public health education.