Evaluation of Humoral Immune Responde in Duchenne Muscular Dystrophy.

• Grant number: 08/02329-1
• Support Opportunities: Scholarships in Brazil - Master
• Start date: August 01, 2008
• End date: February 28, 2010
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Arlete Aparecida Martins Coelho-Castelo
• Grantee: José Eduardo Cury Fiuza
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

The muscular dystrophies are a group of genetic disorders associated with progressive muscular weakness. Among X linked recessive disorders, the most common is the Duchenne Muscular Dystrophy (DMD) and its more slightly variant, Becker Muscular Dystrophy. The DMD is caused by mutations in the dystrophin gene (2.5 Mb), located on the short arm of X chromosome (Xp21), affecting one of 3500 boys. The absence of dystrophin triggers a series of muscle injuries, culminating with necrosis and healing of the muscle fiber, which makes it inactive. Several attempts to correction by gene therapy has been tested and many are still being analyzed, but one of the problems is the fact that dystrophin is encoded by a large gene, containing 80 exons. Although the DMD is a disease classified from the point of genetic view, innumerous experiments have increasingly demonstrated the involvement of components of the immune system in the pathophysiology of the disease. Analysis of muscles of patients and in dystrophyn knockout mice (mdx) shown a lot of serious commitments of muscle fibers, with characteristics of necrosis. Generally, the injured muscles contain huge amounts of macrophages, lymphocytes, both CD4 + T helper and cytotoxic CD8 + T, and NK cells, eosinophils and mast cells. Furthermore, although few studies evaluated the action of the humoral immune response in this disease, it is believed that this has some kind of involvement in the inflammatory process in the muscles. Regardind this this project will develop a mice strain that will have mdx + / + /BKO -/- allowing the analysis of humoral immune response to greater understanding of the disease and develop more effective drugs.