Advances in Therapy for Specific Monogenic Diseases

Goals of this chapter are to present examples of monogenic diseases and reports of preclinical studies and treatment approaches, designed to impact specific gene defects or the downstream effects of gene mutations. It is important to take into account that mutations in a number of different genes may lead to highly similar phenotypes. Several examples of genetic heterogeneity in monogenic diseases are presented. Correct diagnosis and identification of the underlying gene defect are, of course, essential for implementation of gene-based therapies. Treatments of hemoglobinopathies, including sickle cell disease and thalassemias discussed, include standard treatments and new therapeutic approaches. Treatments of Duchenne muscular dystrophy downstream of the gene defect are discussed. A number of preclinical studies and clinical therapies for Rett syndrome, forms of retinitis pigmentosa, Pelizaeus-Merzbacher disease, Charcot-Marie-Tooth neuropathies, and keratin disorders including epidermolysis bullosa are presented. Genetic heterogeneity occurs in all of these disorders.