Methods for Noninvasive Monitoring of Muscle Fiber Survival with an AAV Vector Encoding the mSEAP Reporter Gene

Muscular dystrophies (MD) are a group of genetically and phenotypically heterogeneous inherited disorders characterized by the progressive degeneration of the skeletal muscle tissue. In the last decade, a tremendous amount of studies were performed to test therapeutic strategies in animal models. Evaluation of such strategies requires the use of criteria predictive of their therapeutic relevance. Here we describe a simple, noninvasive assay to monitor muscle degenerative process. An adeno-associated vector encoding a secreted form of murine embryonic alkaline phosphatase (mSEAP) reporter gene is administrated at the time of treatment. The amount of circulating mSEAP will reflect the level of myofiber survival. We tested this assay with therapeutic gene transfer. We found a strong correlation between therapeutic gene expression/muscle disease amelioration and the circulating levels of mSEAP. The assay will be very useful for monitoring muscle cell survival after therapeutic intervention.