Scientists Thursday said they have identified what may be the first step in the process that causes the most common and severe form of muscular dystrophy.
They found that human muscle cells affected by the disease largely lack a protein normally found on the cell surface.Lack of that protein may permit the muscle destruction that marks the disease, the scientists reported in the British journal Nature.
The work dealt with Duchenne muscular dystrophy. It is a genetic disorder that strikes boys almost exclusively, appearing in about one in every 3,500 male births in the United States.
It causes a progressive weakening and wasting of voluntary muscles. Most patients must use wheelchairs by age 12, and most die in their early 20s.
The new work was done by Kevin Campbell and colleagues at the Howard Hughes Medical Institute and department of physiology and biophysics at the University of Iowa College of Medicine.
The researchers followed up a 1987 discovery that the basic defect in muscles affected by Duchenne is the lack of a protein called dystrophin. The protein is missing because of a flaw in the gene that normally tells muscle cells how to produce it.
At the time of the discovery, nobody knew what dystrophin normally does in muscle cells, nor why its absence would cause the disease.
One puzzle was that dystrophin had no apparent connection to the surface of muscle cells, where scientists knew that early abnormalities occurred in Duchenne.
The new work provides that connection, shedding important light on the Duchenne disease process, said Dr. Salvatore DiMauro of Columbia University in New York.
Campbell and colleagues found that dystrophin is normally bound to a complex of four proteins on the surface of muscle cells.
Dystrophin apparently acts to anchor the complex to cytoskeleton, a region of fibrous material beneath the cell surface, Campbell said in a telephone interview.