Duchenne Muscular Dystrophy: Animal Models and Genetic Manipulation

This timely volume assesses recent progress in the search for a curative treatment for Duchenne muscular dystrophy (DMD). Leading international experts highlight important advances in our understanding of dystrophinopathies, discuss the use of animal models in developing therapies for DMD, and analyze experiments in humans and animals on myoblast transfer and direct gene transfer therapy. The papers presented and the critical discussions among the contributing authors define the major problems that need to be addressed in future research.
The opening chapters review the latest studies on the pathological features of Duchenne and Becker muscular dystrophy. the ultrastructural localization and functions of dystrophin, and normal and abnormal dystrophin gene expression. The contributors then describe and compare two different animal models of Duchenne muscular dystrophy: the xmd dog, which exhibits skeletal muscular dystrophy similar to human DMD, and the mdx mouse, which shares the genetic dystrophin defect underlying the disease, but does not develop severe progressive skeletal myopathy. Full consideration is given to the relevance of both animal models in defining the mechanisms of muscular dystrophy and evaluating therapeutic strategies.
A major portion of the book focuses on experiments with myoblast transfer in DMD patients and in animals. Noted investigators detail methods for determining the extent to which transplanted non-dystrophic myoblasts survive within the host, fuse with dystrophic muscle, correct the dystrophin defect, arrest the pathological changes in the host muscle, and prevent or slow the progressive loss of muscle function. The contributors also explore new approaches to direct gene transfer in DMD and assess the relative feasibility of donor myoblast transfer, direct gene transfer, and patient myoblast-mediated gene transfer.
This volume offers much-needed direction to researchers developing therapies for Duchenne and Becker muscular dystrophy. It will also be a valuable stimulus to scientists investigating other muscular dystrophies and genetic diseases.