Cytoskeletal Defects in Avian Muscular Dystrophy

Since there is at present no effective form of chemotherapy available to humans affected with the major types of muscular dystrophy, hereditary and experimentally induced animal models have been extensively studied to gain information about beneficial effects of various pharmacological agents and to study nerve-muscle interactions with respect to structure and function. None of the animal models, however, is directly comparable to any of the human dystrophies, and analogies drawn between them can be very misleading. However, the genetically dystrophic chicken provides a convenient model for testing drugs that may be of benefit even though the primary lesions in these animals are unknown and their relevance to human muscular dystrophies is unclear. Despite these drawbacks, the dystrophic-chicken model is an especially promising system for the study of genetically inherited myopathies because the progressive developmental onset of the disease closely mimics the human form of Duchenne muscular dystrophy in the areas of histological signs of muscle degeneration, muscle-enzyme leakage into blood, and progressive loss of functional ability. Because of the large number of similarities that the avian model of muscular dystrophy shares with Duchenne muscular dystrophy, chemotherapeutic trials in chickens can assess quantitative and qualitative parameters before clinical trials are initiated. In this chapter, both morphological and biochemical data will be presented to document a cyto-skeletal defect in avian muscular dystrophy. Isaxonine, a recently synthesized drug, retards the developmental pathological processes in the dystrophic chicken. It will be shown that by daily injection of this chemotherapeutic agent, the cytoskeletal defect in avian muscular dystrophy is corrected.