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Mechanisms of protection in Duchenne Muscular Dystrophy: metabolic analysis of the extraocular muscles and diaphragm of young and old mdx mice

Grant number: 23/07033-3
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2023
Effective date (End): October 31, 2024
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Cintia Yuri Matsumura
Grantee:Estela Kato dos Santos
Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Duchenne muscular dystrophy (DMD) is a lethal pediatric muscle disease that leads to progressive weakness and wasting of the skeletal and cardiac striated muscles. It is characterized by the absence or low expression of dystrophin, leading to recurrent muscle fiber damage, chronic inflammation, and fibrosis. The mdx mouse is a commonly used model in DMD research due to its similarity in the disease's reproduction and evolution. The diaphragm (DIA) of the mdx mouse is the muscle most closely resembles human dystrophic and is the most severely affected due to its constant workload, being highly relevant to the study of DMD. However, skeletal muscles do not have a standard response to the progression of muscle pathology, as observed in extraocular muscles (EOM) that are structurally and functionally protected. Through the interaction between dystrophinopathy and changes in metabolites, and with the help of metabolomics, it is feasible to identify biomarkers for diagnosis and monitoring of the disease and better understand the mechanisms of protection. In our laboratory, we have studied the tongue of young and old mdx by histology and metabolomics and it was possible to identify biomarkers related to muscle protection. Thus, the proposed project aims to study the metabolites of the diaphragm and extraocular muscles of the mdx mouse in variable age and dystrophic progression to establish biomarkers of the aggressive phenotype and its mechanisms of protection, which are not yet fully understood, to assist in the diagnosis and monitoring of the pathology, future researches, as well as development of new therapies.

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