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Therapeutic approaches in an experimental model of muscular dystrophy

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Author(s):
Carlos Roberto Bueno Júnior
Total Authors: 1
Document type: Doctoral Thesis
Press: São Paulo.
Institution: Universidade de São Paulo (USP). Instituto de Biociências (IBIOC/SB)
Defense date:
Examining board members:
Mayana Zatz; Luciana Amaral Haddad; Alessandra Medeiros; Oswaldo Keith Okamoto; Paulo Rizzo Ramires
Advisor: Mayana Zatz
Abstract

Muscular dystrophies are genetic diseases caused by mutations in different genes. They are characterized by muscle degeneration, motor prejudices and, generally, early death. Among them, Duchenne muscular dystrophy (DMD) is the most common and severe form and it is caused by mutations in the dystrophin gene. The most widely used animal model of DMD is the MDX mouse. The aim of this study was to test four potential therapeutic approaches assigned in two experiments: 1. voluntary exercise training in activity road and/or AMPK and PPAR agonists drugs every other day in MDX mice (AICAR: 100 mg.Kg-1.day-1, IP; GW 1516: 5 mg.Kg-1.day-1, gavage); 2. Intravenous injection of stromal stem cells from human adipose tissue (106 cells every 10 days in the first two months and monthly injections in the following four months) and/or alanine and glutamine amino acids supplementation (10 mg.Kg-1.day-1, daily IP injections). In the first experiment we demonstrated that mdx mice submitted to exercise training associated to drugs presented improved muscle function when compared to the other groups. In the second experiment, on the other hand, it was observed that the animals submitted to cell therapy presented increased survival when compared to non injected animals and animals treated with both approaches. These results, here demonstrated for the first time, can contribute to understand the physiopathology of muscular dystrophies and may give insights for future therapeutic approaches (AU)