Therapeutic Potential of Resistance Training for Muscle Regeneration and Quality of Life in ALS

• Grant number: 24/22589-0
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: September 01, 2025
• End date: August 31, 2026
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Adelino Sanchez Ramos da Silva
• Grantee: Bruno Brieda Marafon
• Supervisor: Antonio Musaro
• Host Institution: Escola de Educação Física e Esporte de Ribeirão Preto (EEFERP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: Università degli Studi di Roma La Sapienza, Italy
• Associated to the scholarship: 22/09100-7 - Role of rev-erb-alpha in aging-associated endoplasmic reticulum stress, BP.DR

Abstract

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by the loss of motor neurons, leading to severe muscle atrophy, paralysis, and, ultimately, death due to respiratory failure. Genetic mutations are a major etiopathogenic factor in ALS and have led to the development of animal models, such as the SOD1G93A transgenic mouse, which replicates the disease's clinical features. Although some pharmacological treatments offer limited survival benefits, nonpharmacological interventions, including invasive ventilation, have shown some efficacy in prolonging life. Recent evidence suggests that chronic physical exercise (CPE) may offer additional therapeutic potential, delaying the onset of the disease in SOD1 mutant animals. CPE stimulates mitochondrial biogenesis, enhances blood flow, and increases muscle regenerative capacity by activating satellite cells and promoting the release of growth factors like insulin-like growth factor 1 (IGF-1). Such adaptations improve tissue oxygenation, energy production, and repair processes, which could support motor function preservation in ALS. While previous studies have linked active lifestyles to ALS risk, recent findings indicate that physical activity is not necessarily a risk factor but may confer therapeutic advantages. Notably, the impact of resistance training on muscle regeneration in SOD1G93A transgenic mouse remains underexplored. This study aims to investigate CPE, particularly resistance training, as a therapeutic approach to muscle regeneration and symptom management in ALS, focusing on improving quality of life and longevity. The findings may support CPE as a nonpharmacological strategy that complement existing ALS treatments, offering insights into new therapeutic possibilities for managing this devastating disease.