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Study of dystrophin and TNF-alpha in GMRD dogs during treatment with multi-drugs through analysis of PCR

Grant number: 11/14265-0
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): May 01, 2012
Effective date (End): April 30, 2013
Field of knowledge:Agronomical Sciences - Veterinary Medicine
Principal Investigator:Maria Angelica Miglino
Grantee:Marília Alves Ferreira
Home Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Muscular dystrophies are a group of inherited disorders that cause muscle weakness of varying severity. The Duchenne muscular dystrophy (DMD) is the most serious and common, besides a more rapid progression among the hereditary myopathies. This degenerative disease is caused by mutation in the gene encoding the protein dystrophin. The Duchenne muscular dystrophy, affecting 1 in every 3500 children born, is homologous to muscular dystrophy in dogs Golden Retriever (GRMD). The similarity of clinical manifestations justifies the use of dogs as experimental models for the series of studies aimed at developing treatments for children affected by the disease. Dystrophin is a transmembrane protein complex that maintains the mechanical stability of the sarcolemma. Its deficiency leads to greater susceptibility to muscle damage induced by exercise. The tumor necrosis factor (TNF-alfa) is a proinflammatory cytokine produced by the immune system, however, overexpressed in dystrophic individuals, contributing to an inflammatory reaction related to the progression of secondary dystrophinopathies. In this paper, using different drugs, including: Sildenafil, related to increased nitric oxide, ursodeoxycholic acid, an anti-inflammatory; acetylcysteine, an antioxidant, losartan, an antifibrotic, Mycophenolate mofetil, immunosuppression, thalidomide, anti TNF-alfa and diltiazem, blockers of calcium channels. Used concomitantly, makes up a cocktail of drugs whose purpose is the treatment of the deleterious effects caused by the disease, thus providing a better quality and survival of dystrophic patients. Will be used 6 male dogs affected by Duchenne muscular dystrophy (GRMD) between these four will receive multifármacos and 2 are controls, and 3 normal male dogs and normal standards do not undergo any treatment, from 60 days to 1 year of age, those belonging to the group of animals kennel GRMD Brazil located in Department of Anatomy and Surgery FMVZ-USP.