4. Gene Therapy of Duchenne Muscular Dystrophy

Publisher Summary This chapter reviews the gene therapy of Duchenne muscular dystrophy (DMD). DMD is an X-linked disorder affecting about 1:3500 live male births. It is a more complex disease involving the heart and the central nervous system (CNS), as well as peripheral nerves and smooth muscle; it is generally noticed between the ages of 2 and 5 years. Skeletal muscle is the tissue with the most striking pathology in patients lacking dystrophin, but heart and central nervous system (CNS) may also be affected. More recent studies using magnetic resonance spectroscopy indicate that DMD patients have significant higher values than controls in the brain ratios of inorganic phosphate to ATP to phosphomonoesters, and to phosphocreatine. Animal models are becoming increasingly important in testing potential therapeutic approaches for DMD. Histopathologic analysis of skeletal muscle appears to be the easiest and most reliable way of assessing the efficacy of dystrophin gene replacement, particularly if the analysis is carried out in the diaphragm.