Nintedanib Reduces Muscle Fibrosis and Improves Muscle Function of the Alpha-Sarcoglycan-Deficient Mice

Area of Science:

• Biomedical research
• Muscular dystrophy research
• Pharmacological interventions

Background:

• Sarcoglycanopathies are inherited muscle disorders causing progressive weakness due to sarcolemma instability.
• Muscle fiber injury, loss, and replacement by fibro-adipose tissue characterize these conditions.
• Reducing fibro-adipose tissue expansion is a potential therapeutic strategy.

Purpose of the Study:

• To investigate the therapeutic effect of nintedanib in a mouse model of alpha-sarcoglycanopathy.
• To assess nintedanib's impact on muscle function, histology, and molecular profiles.
• To evaluate nintedanib's potential as a treatment for sarcoglycanopathies.

Main Methods:

• Alpha-sarcoglycan-deficient (Sgca-/-) mice were treated with nintedanib or vehicle for 10 weeks.
• Muscle function was evaluated using treadmill tests and grip strength.
• Histological, cardiac, proteomic, and transcriptomic analyses were performed.

Main Results:

• Nintedanib treatment improved treadmill performance and grip strength in Sgca-/- mice.
• Histological analysis revealed reduced muscle degeneration and fibrosis in nintedanib-treated mice.
• Proteomic and transcriptomic data indicated a reversion of the inflammatory cytokine profile.

Conclusions:

• Nintedanib effectively improved muscle function and architecture in an alpha-sarcoglycanopathy mouse model.
• The drug reduced muscle fibrosis and degeneration, mitigating the chronic inflammatory environment.
• Nintedanib shows promise as a potential therapeutic agent for alpha-sarcoglycanopathy.