Duchenne Muscular Dystrophy is the most common and severe of the human muscular dystrophies, affecting 1 in 3,500 live male births. It is characterized by progressive skeletal muscle weakness and death occurring in late teens to early 20's, usually from respiratory complications secondary to diaphragmatic dysfunction. Therapeutic stretegies that focus on delivering cells, genes, or proteins to the dystrophic musculature have been limited but muscular dystrophy related cardiomyopathy has been successfully treated by cardiac transplantation. Our broad objective is to translate the success of solid organ transplantation toward the palliation of respiratory failure by transplanting the main muscle of respiration. We have generated preliminary data demonstrating the feasibility of diaphragmatic transplantation in a rodent model and our specific aims are: 1)To evaluate long-term diaphragmatic survival after transplantation into genetically identical host. We will specifically evaluate blood flow, myocyte survival, and fibrosis. 2)To evaluate innervation of the diaphragmatic graft. We will specifically focus on histologic and functional evidence of reinnervation in several experimental conditions. 3)To evaluate the motor function of the diaphragmatic graft. We will test the motor function of the transplanted graft using both in vivo and ex vivo preparations. At the completion of these experiments we hope to further define the potential of diaphragmatic transplantation as a therapeutic strategy for the treatment of Duchenne Muscular Dystrophy as well as to identify potential pitfalls in a rodent model.
| Krupnick, Alexander Sasha; Gelman, Andrew E; Okazaki, Mikio et al. (2008) The feasibility of diaphragmatic transplantation as potential therapy for treatment of respiratory failure associated with Duchenne muscular dystrophy: acute canine model. J Thorac Cardiovasc Surg 135:1398-9 |
