Multi-drugs therapies on pulmonary respiration, gait analysis and levels of calcium related proteins in dystrophic mdx mice

• Grant number: 22/15510-3
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: April 01, 2023
• End date: March 31, 2024
• Field of knowledge: Biological Sciences - Morphology - Anatomy
• Principal Investigator: Renato Ferretti
• Grantee: Bruno dos Santos Ricardi
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Duchenne muscular dystrophy (DMD) is a severe, progressive, X-linked muscle disease caused by the loss of dystrophin. DMD is associated with muscle necrosis, degeneration, inflammation, fat replacement, and fibrosis, resulting in muscle weakness, cardiorespiratory failure, and premature death. There is no curative therapy. Investigations into disease mechanisms offer an opportunity to identify new therapeutic targets for the treatment of DMD. The most crucial secondary event in the dystrophin-deficient muscle is the abnormal intracellular calcium concentration (iCa2+), which contributes to disease progression in DMD. The recommended therapeutic strategies combine multiple drugs in the protein expression and regulation of Ca2+ homeostasis in dystrophic muscles. In the present study, we aim to evaluate the effect of multidrug treatments on dystrophic muscle fibers of mdx mice. We will use in vivo assays to verify lung ventilatory function, gait analysis, and biochemical, histopathological, and protein assays. We intend to demonstrate the positive effects of combined therapies in reducing myonecrosis in dystrophic muscles. Functional (pulmonary ventilation and gait patterns), histopathological and molecular improvement of the musculature after different therapies, we intend to contribute to future applications in medium-sized animals and for the treatment of patients with DMD.