Utilisation de l'IGF-1 et d'un dérivé peptidique synthétique pour favoriser le succès d'un traitement contre la dystrophie musculaire de Duchenne

Authors: Mills, Philippe
Advisor: Tremblay, Jacques-P.
Abstract: Duchenne muscular dystrophy (DMD) is a degenerative disease that affects young boys. The absence of the dystrophin, a protein located on the surface of the muscular fibers, contributes to muscle weakness that characterizes the disease. Many approaches are considered not only to slow down the progression but also to treat Duchenne myopathy. Myogenic cell or myoblast transplantation is an avenue which enables the reintroduction of the normal dystrophin gene in the affected muscles. The procedure consists of injecting normal cells, which contain the normal dystrophin gene, to the patients. Unfortunatly, some problems are associated with this approach. In fact, a massive cellular lost is observed during the days just after the graft. The injection of large quantities of myoblasts can make up for this quantitative deficit. Moreover, the myogenic cells do not migrate a lot when they are injected in the muscle. It is therefore necessary to make multiple close injections in order to treat an entire muscle. Growth factors are small peptides that can modulate many cellular activities. The insulin-like growth factor (IGF-1) favours myogenic cells proliferation, differentiation and survival. IGF-1 possesses many isoforms like the mechano growth factor (MGF). The results presented in this thesis demonstrate that a synthetic peptide within the MGF also favours myoblast proliferation. New pro-migratory functions have been demonstrated for both IGF-1 and MGF synthetic peptide. Indeed, they are both able to promote in vivo migration of human myogenic cells by modulating important proteolytic systems. On the other hand, my results have also demonstrated that the MGF peptide can increase the transplantation success when murine receivers are treated by intramuscular injections or systemic administration. This improvement is possibly caused by the MGF peptide pro-mitogenic capacity which could compensate for the initial cell lost. IGF-1 and MGF synthetic peptide could be used to help diminish the number of injections required to treat a muscle while contributing to myoblast transplantation success in patients affected by Duchenne muscular dystrophy.
Document Type: Thèse de doctorat
Issue Date: 2007
Open Access Date: 13 April 2018
Permalink: http://hdl.handle.net/20.500.11794/19664
Grantor: Université Laval
Collection:Thèses et mémoires

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