Modulating Fibro/Adipogenic Precursors to Prevent Adipogenic Replacement of Muscle

ABSTRACT. Successful muscle regeneration requires an elaborate cellular choreography between multiple cell populations to remove and replace damaged fibers. Disruption of this choreography leads to muscle degeneration and fibrotic or adipogenic replacement of myofibers. This phenomenon is particularly prevalent in muscular dystrophies, where progressive muscle loss leads to severe debilitation and early loss of life. Hence, there is growing need to understand the cell populations and their interactions which contribute to myofiber regeneration, but can lead to fibrotic or adipogenic replacement when gone awry. This project aims to understand the mechanism underlying impaired cellular interactions leading to myofiber loss and muscle weakness in limb girdle muscular dystrophy type 2B and test approaches to prevent this impairment. This understanding will help develop novel targeted therapeutic approaches to arrest disease progression in this and other muscular dystrophies that are currently without effective treatment options.