Treatment with Galectin-1 improves myogenesis and membrane repair in dysferlin-deficient models.


Translational Research

Poster Number: 43


Mary Vallecillo-Zúniga , Mattew Rathgeber MSc, Daniel Poulson , Spencer Hayes , Christian Arnold , Braden Kartchner , Hailie Gill , Jacob Luddington


1. Brigham Young University, 2. BYU, 3. Brigham Young Univeristy, 4. BYU, 5. Brigham Young University, 6. Brigham Young University, 7. Brigham Young University, 8. Brigham Young University

Muscular dystrophies are a heterogeneous group of genetic diseases involving mutations in genes that compromise sarcolemma stability, muscle strength, and repair. Limb-girdle muscular dystrophy type 2B (LGMD2B) is a type of dysferlinopathy caused by mutations in encoding of the dysferlin protein and is characterized by the following: diminished membrane repair, delayed removal of necrotic muscle fibers, loss of calcium sensitivity leading to signaling mis-regulation, muscle atrophy, malformation of transverse tubule structure and increased inflammatory infiltrate. LGMD2B has an incidence of 1/100,000-1/200,000 depending on geographic location and ethnic background. The lack of a cure and treatment options for LGMD2B patients requires increased research to develop therapeutics to decrease disease progression. Galectin-1 (Gal-1) is a small 14.5 kDa protein with a carbohydrate recognition domain capable of stabilizing the sarcolemma by increasing levels of ECM proteins. Gal-1 has been proven to improve muscle repair capacity in Duchenne muscular dystrophy (DMD) models by increasing extracellular interaction resulted in healthier muscle fibers. Our hypothesis is that Gal-1 increases membrane repair capacity and myogenic potential of dysferlin-deficient muscle cells and muscle fibers. We used recombinant human galectin-1 (rHsGal-1) to treat dysferlin-deficient models. We found that rHsGal-1 treatment for a 48 – 72 h period promotes myogenic maturation with enhancements in size, myotube alignment, and membrane repair capacity in both dysferlin-deficient myotubes and myofibers. Additionally, we discovered that the carbohydrate recognition domain of Gal-1 is necessary for observed membrane repair. Furthermore, membrane repair with rHsGal-1 treatment in dysferlin-deficient and wild-type myotubes and myofibers was calcium-independent. Similarly, one-month in vivo treatment with rHsGal-1 revealed significant improvement in membrane repair capability. Together, our results reveal Gal-1 mediates membrane repair capacity in dysferlin deficient models and increases markers for myogenesis, thus indicting an efficacy in using Gal-1 as a new protein treatment in LGMD2B.