verbatim) The goal of this BRP is to utilize a number of aspects of bioengineering in order to develop tools and therapeutics for the treatment and monitoring of muscular dystrophies. The project is collaboration between three investigators and includes the following areas of bioengineering relevant to the PA: 1) cell and tissue engineering, 2) imaging and 3) therapeutics. Collectively we will delineate factors that when expressed in muscle may slow that rate of degeneration that is concomitant with either the complete (Duchenne muscular dystrophy) or partial (Becker muscular dystrophy) loss of dystrophin. These studies will utilize the mdx mouse as the animal model for dystrophin deficiency. The long-term goal is to gain the understanding and tools necessary to develop adeno-associated (AAV)-based gene therapy for Duchenne and Becker muscular dystrophies. Three parallel lines of investigation (each directed by one of the three investigators) are proposed: Section 1: a dissection the mechanical role of dystrophin and muscle adhesion proteins (directed by Dennis Discher); Section 2: an assessment of the functional benefits of restoring adhesion molecules to dystrophic muscle using recombinant adeno-associated virus gene delivery (directed by H. Lee Sweeney, Ph.D.); and Section 3: development of non-invasive methods for monitoring therapeutic benefits of dystrophin gene transfer (directed by Glenn Walter, Ph.D.).
| Pacak, Christina A; Walter, Glenn A; Gaidosh, Gabe et al. (2007) Long-term skeletal muscle protection after gene transfer in a mouse model of LGMD-2D. Mol Ther 15:1775-81 |
| Frimel, Tiffany N; Kapadia, Fatema; Gaidosh, Gabriel S et al. (2005) A model of muscle atrophy using cast immobilization in mice. Muscle Nerve 32:672-4 |
| Frimel, Tiffany N; Walter, Glenn A; Gibbs, John D et al. (2005) Noninvasive monitoring of muscle damage during reloading following limb disuse. Muscle Nerve 32:605-12 |
| Lee, Sukho; Barton, Elisabeth R; Sweeney, H Lee et al. (2004) Viral expression of insulin-like growth factor-I enhances muscle hypertrophy in resistance-trained rats. J Appl Physiol 96:1097-104 |
| Walter, Glenn A; Cahill, Kevin S; Huard, Johnny et al. (2004) Noninvasive monitoring of stem cell transfer for muscle disorders. Magn Reson Med 51:273-7 |
| Barton, Elisabeth R; Morris, Linda; Musaro, Antonio et al. (2002) Muscle-specific expression of insulin-like growth factor I counters muscle decline in mdx mice. J Cell Biol 157:137-48 |
