Combined therapies on the ventilatory pattern, locomotion, and levels of calcium-related proteins in dystrophic mdx mice

• Grant number: 23/04100-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): August 01, 2023
• Effective date (End): July 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Renato Ferretti
• Grantee: Vitória Luíza Alves de Souza Rios
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

There is no curative treatment for Duchenne muscular dystrophy (DMD) which is a severe and progressive X-linked muscle disease caused by loss of dystrophin. DMD is associated with muscle degeneration, necrosis, inflammation, fat replacement and fibrosis, which results in muscle weakness, cardiorespiratory failure and premature death. The most important secondary event is the abnormal elevation of intracellular calcium concentration in dystrophin-deficient muscle, which contributes to disease progression in DMD. Therapeutic strategies should prioritize the combination of multiple drugs in protein expression and regulation of Ca2+ homeostasis in dystrophic muscles. In the present work, we intend to evaluate the effect of multi-drug treatments (Predinison, omega-3 and calcium blocker) in dystrophic muscle fibers of mdx mice. We will use in vivo assays to verify pulmonary ventilatory function, analysis of locomotion patterns (gait), biochemical, histopathological and protein assays in dystrophic muscles of mdx mice. We intend to demonstrate the positive effect of combined therapies on functional, biochemical, cellular and molecular parameters in dystrophic mice. With the functional and molecular improvement of the musculature after the treatments, we hope to contribute to future applications in medium-sized animals and for the treatment of patients with DMD.