Stimulation de la régénération endogène dans le traitement de la dystrophie musculaire

Muscular dystrophies are severe, degenerative diseases for which no efficient therapeutic options exist. These diseases are characterized by muscle wasting, limited life expectancy and reduced ambulatory capacities. Mutations in proteins implicated in the attachment of muscle fibers to the extracellular matrix cause the fibers to be more fragile, making them more susceptible to rupture under physical stress. Asynchronous multifocal cycles of degeneration and regeneration of the muscle leads to chronic inflammation, stem cell exhaustion, and fibrotic tissue accumulation ultimately impairing muscle function severely. Up to this day, experimental treatments have all met various pitfalls and none have reached the clinics. Thus, research into novel viable approaches to alleviate diseases symptoms is much needed. Here, we propose a novel treatment approach for muscular dystrophy, that is centered on stimulating muscle stem cell (MuSC) function which leads to an increase in the endogenous regenerative capacity allowing to maintain muscle function. We describe the use of Apelin-13 as a potential candidate for the treatment of muscular dystrophy. Apelin is an endogenous peptide that has been studied for many years in relation to its beneficial effect on the cardiovascular system and its anti-diabetic effects in mice. More recently, Apelin has also been shown to be a MuSC stimulatory factor. We show here that systemic Apelin-13 administration stimulates MuSC numbers and boosts skeletal muscle regeneration and thereby increases motor function in the DyW/DyW model of Congenital Muscular Dystrophy. No adverse effects were observed, and Apelin-13 treatment was well tolerated in mice. This discovery is of major importance considering the absence of alternative efficient treatments for these severe degenerative diseases. There is great translational potential associated with this research as many compagnies have grown interest in rare disease research over the last decade. A drug with a beneficial impact on disease state in muscular dystrophy could have drastic effects on the life of patients.

Name thesis:degree_name

M. Sc.

Level thesis:degree_level

Maîtrise

Discipline thesis:degree_discipline

Pharmacologie

Grantor dc:publisher

Université de Sherbrooke

Year dc:date.issued

2019

Author dc:creator

• Collerette-Tremblay, Jasmin

Advisors dc:contributor.advisor

• Bentzinger, Florian
• Auger-Messier, Mannix

• Dystrophie musculaire
• Maladies rares
• Régéné ation tissulaire
• Cellules souches musculaires
• Pharmacothérapie
• Système apélinergique
• Muscular dystrophy
• Rare diseases
• Tissue regeneration
• Muscle stem cells
• Pharmacotherapy
• Apelinergic axis

Language dc:language.iso

fr

Handle dc:identifier.uri

http://hdl.handle.net/11143/20511

OAI identifier oai:identifier

oai:usherbrooke.scholaris.ca:11143/20511