Skeletal muscle is the largest organ in the body by mass and provides force generation and mobility. Muscle plays a highly-specialized role in assisting in the regulation of the body's metabolism and is a key target of insulin. Consequently, diseases that affect muscle function can have severe and broad effects.

Many different medical conditions and their treatments contribute to loss of muscle mass or atrophy, including:

• Deteriorating nerve function
• Immobilization or prolonged bed rest
• Glucocorticoid drugs
• The wasting associated with AIDs and cancer cachexia
• Sarcopenia, the normal atrophy that accompanies aging, also promotes debilitating frailty in many older patients

In all of these settings, patients often have few therapeutic choices to prevent muscle loss. Multidisciplinary teams of Regeneron scientists are working together to discover new potential therapies to treat or cure muscle disorders.

Cellular Signals Mediate Balance Between Muscle Hypertrophy and Atrophy

Muscle size is maintained by the delicate balance between two processes that:

1. Promote muscle growth (hypertrophy) by increasing protein synthesis
2. Cause muscle atrophy by initiating protein breakdown

The cellular signals in muscle tissue that initiate muscle protein synthesis and breakdown are only now beginning to be understood. Regeneron scientists have identified both the key cellular proteins that mediate the muscle growth process, and also proteins required for muscle atrophy.

• Based on these advances, Regeneron is developing a number of novel therapeutic candidates to inhibit muscle atrophy, including VelocImmune^® fully-human monoclonal antibodies and other therapeutic proteins.
• These molecules also show promise in laboratory experiments in correcting imbalances of metabolism, such as the insulin resistance that characterizes diabetes.