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Analysis of tongue's metabolic profile and gene therapy on the mdx mice

Grant number: 19/20162-1
Support type:Scholarships abroad - Research Internship - Scientific Initiation
Effective date (Start): December 01, 2019
Effective date (End): February 29, 2020
Field of knowledge:Biological Sciences - Morphology - Anatomy
Principal Investigator:Cintia Yuri Matsumura
Grantee:Marcelo dos Santos Voltani Lorena
Supervisor abroad: Jeffrey S Chamberlain
Home Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
Local de pesquisa : University of Washington, United States  
Associated to the scholarship:18/25598-0 - Biomarkers for Duchenne Muscular Dystrophy: study of tongue in young and old mdx mice, BP.IC

Abstract

Duchenne Muscular Dystrophy (DMD) is an X chromosome-linked and the most common hereditary muscular disease in childhood. Mutation in the DMD gene leads to the absence of dystrophin, a subsarcolemmal protein, which is part of dystrophin-glycoproteins complex (DGC). The mdx mice, DMD model, shows the first signs of degeneration around 20 days of age and around 26 months of age shows typical dystrophic signs, such as loss of muscle fibers, increased fibrosis and increased regenerated fibers. The tongue (TON) of these mice exhibits unusual behavior. Inflammatory cells were hardly found in TON and its collagen expression did not change at 3 months of age. However, at 26 months of age, was the second most affected muscle by fibrosis and loss of muscle fibers, similar to the diaphragm muscle (DIA). Metabolomics provides an integrated view of biochemistry and establishes biomarkers of metabolic profiles for certain disease conditions. Studies using the mdx present changes in metabolites related to myonecrosis progression. Gene therapies using adeno-associated viral (AAV) vectors have advanced into clinical trials for several diseases, including DMD, where the treatment with the micro-dystrophins (µDys) in mice had displayed significant function, as increased force generation and neuronal nitric oxide synthase in sarcolemma, proving to be an option to be studied. This project will provide improving a molecular knowledge about DMD's metabolic profile. As we characterized mdx tongue as a protected muscle, studying tongue's metabolic profile will provide biomarkers for the DMD muscle protection and knowledge for further treatments for DMD patients.