University of Maryland (UM) researchers and collaborators report in the journal Science Signaling that skeletal muscle degeneration in Duchenne muscular dystrophy (DMD) is worsened by stiffening of the microtubule cytoskeleton that provides structure inside muscle cells.

Duchenne muscular dystrophy occurs in about 1 out of every 3,600 male infants and "worsens quickly," according to the U.S. National Library of Medicine. It is caused by a defective gene for a protein (dystrophin) in the muscles and there is no known cure.

The unique interdisciplinary study identifies new potential therapeutic targets for intervening in this devastating disease, says Christopher Ward, PhD, associate professor at the UM School of Nursing and senior author of the study.

"We show that an enhancement in the microtubule network structure, a stiffening, underlies dysfunction in Duchenne muscular dystrophy," says Ward.

The study is a follow-up to the discovery by Ward and others (Prosser et al. Science, 333, 2011) of a new signaling pathway called X-ROS signaling. It is a pathway by which the mechanic stress of stretching a muscle cell acts through the microtubule network to activate a small burst of reactive oxygen species (ROS), which is also known as free radicals.

"In the current study, we revealed that an increase in the density of the microtubule network is a critical factor in the excessive activation of X-ROS signaling in a mouse model." says Ward. He further explains "antagonizing the microtubule network or components of the X-ROS pathway reduced muscle damage in the mouse DMD model."

Based on the finding, the authors believe that the microtubule network and X-ROS pathway may be potential therapeutic targets for treating Duchenne muscular dystrophy.

To strengthen that premise the authors also conducted an analysis of genes expressed in human muscle samples from DMD patients, concerning X-ROS related molecular activity. "This additional finding provides a bridge to the human disease and reinforces the microtubule network and X-ROS as potential therapeutic targets" says Susan Dorsey, PhD, RN, FAAN, associate dean for research at the School of Nursing and co-corresponding author on the study who led the analysis.

The current study was an interdisciplinary collaboration between colleagues of the School of Nursing and School of Medicine at the University of Maryland in Baltimore. Additional authors were from the Center for Genetic Medicine at Children's National Medical Center in Washington, D.C., George Washington University, University of Buffalo, and from the Department of Biophysical and Electronic Engineering, Universitý di Genova, Italy. The study was funded by grants from the National Institutes of Health.