The human body has evolved with an ability to rapidly adapt to physical challenges by allowing controlled injury and repair of skeletal muscle as a way to increase muscle size and strength. Different skeletal muscle fiber populations exhibit different thresholds for this type of remodeling with an aim towards maximizing the speed of adaptation while minimizing the potential for detrimental effects on existing function. In serious inherited muscle diseases such as Duchenne and Becker muscular dystrophy, loss or mutation of the supportive muscle protein dystrophin results in an amplification of adaptive injury processes and uncontrolled damage in response to normal daily activities. With time, this leads to fibrosis, muscle loss, disability, and early death from cardiac or respiratory muscle weakness.
In this presentation, Russell describes how muscle has evolved into two major fiber populations – fast and slow, and his thoughts on why one of these populations, the fast fibers, are more susceptible to injury. He will detail how loss of dystrophin amplifies activity-driven muscle injury and how the nature of this injury creates an opportunity for a novel medicine to improve muscle health in these devastating diseases. To evaluate how this therapeutic approach impacts muscle health, Russelll also describes how proteomic profiling can be leveraged to measure muscle injury signatures in Becker muscular dystrophy.
Co-Founder and Chief Scientific Officer of Edgewise TherapeuticView Slides
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