Galectin-1: A potential protein therapy for Limb Girdle Muscular Dystrophy type 2B
Our scientific rationale is built on prior reports that galectin-1 can increase muscle stability and decrease inflammation which will lead to improved muscle membrane repair. Our preliminary data provides the first evidence demonstrating the ability of Gal-1 to favorably improve LGMD2B disease progression by increasing membrane repair capacity after laser injury, increasing muscle formation and decreasing inflammatory markers. Our proposal will define Galectin-1 as a favorable suppressor of LGMD2B disease pathogenesis and define the mechanism through which these changes are accomplished. Since there are different biochemical forms of Galectin-1 (each known to have unique functions), it is crucial to define the biochemical requirements responsible for therapeutic benefit in LGMD2B. Chronic muscle inflammation is a significant disease characteristic in LGMD2B.1, 2 We will measure the changes in inflammation (macrophage polarization) with Galectin-1 treatment. This proposal uses models of LGMD2B to test the hypothesis that Gal-1 treatment decreases disease pathology by increasing membrane repair capacity and shifting immune homeostasis away from chronic inflammation. Successful completion of this project will define key biochemical characteristics of Galectin-1 necessary for increasing membrane repair and the impact of Galectin-1 on inflammation in LGMD2B. In doing so, these studies will provide new insight into Galectin-1 as a therapeutic for LGMD2B.