Scientists Uncover New Clues to Nemaline Myopathy

MDA research grantee Alan Beggs at Children’s Hospital in Boston led a team that studied a mouse model of one form of nemaline myopathy, a muscle disorder that takes its name from the presence of nemaline (threadlike) rods in muscle fibers, and uncovered two molecular pathways that they say are probably important clues to understanding this disease.

The researchers, who published their findings in the Sept. 1 issue of Human Molecular Genetics, bred mice with a mutation in the gene for the muscle protein alpha-tropomyosin. The mutation is one of the causes of human nemaline myopathy.

By analyzing the molecular content and biochemistry of muscle fibers in mice with and without the alpha-tropomyosin mutation, the researchers discovered that this form of nemaline myopathy is characterized by two processes -- a low rate of muscle fiber degeneration and partial repair; and a failure of cells in the respiratory diaphragm to mature properly.

There was no relationship between the presence or number of nemaline rods in the fibers and deleterious effects on muscle.

The investigators used a technique that measures the activity of genes other than the gene in which the disease-causing mutation is located. These changes in gene activity result in levels of cellular proteins that are either higher or lower than normal and provide a map of the major downstream effects on cells and tissues of the primary mutation.

“These results highlight a previously unrecognized aspect of this disorder, as muscle repair was not known to be a feature of nemaline myopathy,” Dr. Beggs said.

The researchers hope that a better understanding of these molecular abnormalities will one day lead to discovery of an effective treatment for this and other similar congenital myopathies.