Skeletal Muscle Function and Atrophy

Skeletal muscle is composed of different groups of myofibers that are able to remodel in response to injury or stress. Skeletal muscle atrophy can be caused by spinal cord injury and neuromuscular disorders, such as Amyotrophic Lateral Sclerosis (ALS) or Lou Gehrig’s disease, which result in the degeneration of neuromuscular synapses.

Neuromuscular synapses are the structural and functional mediators of cellular signaling between the nervous system and target muscles. Abnormalities in the regulation of neuromuscular gene expression often result in neuropathies and myopathies, disrupting the intimate communication between muscle and motor nerve. Understanding the molecular mechanisms that regulate gene expression at the neuromuscular synapse may lead to new therapeutic targets to treat neuromuscular disorders. A recent study led by Eric. N. Olson, Ph.D., UT Southwestern Medical Center, demonstrated that miR-206 plays a crucial role in ALS and in neuromuscular synapse regeneration (Williams, Science, 2009). miRagen is the exclusive licensee of intellectual property rights related to this discovery.

Skeletal muscle atrophy results in loss of muscle function and occurs during aging, prolonged bed rest and diverse diseases such as cancer, AIDS and diabetes. In many cases, muscle atrophy is reversible; therefore, understanding the signaling pathways that mediate muscle atrophy is fundamental to the design of therapies to alleviate its symptoms. Recently, miRagen, in collaboration with Eric N. Olson, discovered a class of miRNAs embedded within the contractile protein genes of skeletal muscles to be dominant regulators of muscle strength and performance (van Rooij, Dev Cell., 2009).

A major focus of miRagen’s research effort is to use miRNA-based therapies to maintain muscle strength during disease.