{"id":{"repo_id":"sherbrooke","oai_identifier":"oai:usherbrooke.scholaris.ca:11143/20511"},"canonical_url":"https://search.dev.ndltd.org/etd/sherbrooke/oai:usherbrooke.scholaris.ca:11143/20511","repository":{"repo_id":"sherbrooke","name":"Université de Sherbrooke","base_url":"https://usherbrooke.scholaris.ca/server/oai/request"},"display":{"title":"Stimulation de la régénération endogène dans le traitement de la dystrophie musculaire","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Collerette-Tremblay, Jasmin"],"institution":"Université de Sherbrooke","degree_name":"M. Sc.","degree_level":"Maîtrise","degree_discipline":"Pharmacologie","degree_department":null,"school":null,"contributors":[],"advisors":["Bentzinger, Florian","Auger-Messier, Mannix"],"committee_chairs":[],"committee_members":[],"year":2019,"date_issued":"2019","date_published":"2019","updated_at":"2026-07-27T21:07:28Z","subjects":["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"],"languages":["fr"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/11143/20511","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Bentzinger, Florian","Auger-Messier, Mannix"]},{"key":"dc:creator","label":"Author","values":["Collerette-Tremblay, Jasmin"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2023-07-25T14:39:02Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2023-07-25T14:39:02Z"]},{"key":"dc:date.issued","label":"Date","values":["2019"]},{"key":"dc:publisher","label":"Institution","values":["Université de Sherbrooke"]},{"key":"dc:type","label":"Dc Type","values":["Mémoire de maîtrise"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Pharmacologie"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Maîtrise"]},{"key":"thesis:degree_name","label":"Degree Name","values":["M. 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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.","Les dystrophies musculaires sont des maladies génétiques sévères, dégénératives et incurables. Ces maladies sont caractérisées par une perte de masse musculaire, une diminution de l’espérance de vie ainsi qu’une mobilité limitée. Des mutations dans les protéines responsables de l’attache des fibres musculaires à la matrice extracellulaire rendent les fibres plus fragiles et susceptibles à la rupture lors de la contraction musculaire. Des cycles continus de dégénération et régénération mènent à une inflammation chronique, à l’épuisement des cellules souches, à l’accumulation de tissu fibreux et limitent la fonction du muscle. Puisqu’aucun traitement ne s’est révélé efficace lors d’essais cliniques, l’absence de solutions à ce jour pour alléger les symptômes des patients rend la recherche d’approches alternatives essentielle. Nous proposons ici que la stimulation de la régénération est une nouvelle approche qui permet de restaurer et maintenir la fonction du muscle. Cette étude porte sur l’utilisation de l’Apéline-13, un candidat prometteur pour le traitement de la dystrophie musculaire. L’Apéline-13 est un peptide endogène longtemps étudié pour son rôle dans le contrôle du métabolisme et comme régulateur du système cardiovasculaire chez la souris. Récemment, il a été révélé que l’Apéline-13 stimule la fonction des cellules souches musculaires. Nos résultats montrent que le traitement systémique à l’Apéline-13 mobilise les cellules souches musculaires, augmentant grandement la régénération du muscle squelettique, et améliorant drastiquement les performances motrices dans le modèle de Dystrophie Musculaire Congénitale DyW/DyW. De plus, aucun effet secondaire n’a été observé et le traitement a été bien toléré par les souris. Il s’agit de résultats importants, considérant l’absence de traitements efficaces pour la gestion des dystrophies musculaires. L’industrie pharmaceutique connait aussi un intérêt récent pour la recherche dans le domaine des maladies rares. Un composé avec un effet bénéfique sur l’état de santé dans la dystrophie musculaire pourrait avoir un effet drastique sur la vie des patients."]},{"key":"dc:title","label":"Title","values":["Stimulation de la régénération endogène dans le traitement de la dystrophie musculaire"]}]}],"canonical_facts":{"dc:contributor.advisor":["Bentzinger, Florian","Auger-Messier, Mannix"],"dc:creator":["Collerette-Tremblay, Jasmin"],"dc:date.accessioned":["2023-07-25T14:39:02Z"],"dc:date.available":["2023-07-25T14:39:02Z"],"dc:date.issued":["2019"],"dc:description.abstract":["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.","Les dystrophies musculaires sont des maladies génétiques sévères, dégénératives et incurables. Ces maladies sont caractérisées par une perte de masse musculaire, une diminution de l’espérance de vie ainsi qu’une mobilité limitée. Des mutations dans les protéines responsables de l’attache des fibres musculaires à la matrice extracellulaire rendent les fibres plus fragiles et susceptibles à la rupture lors de la contraction musculaire. Des cycles continus de dégénération et régénération mènent à une inflammation chronique, à l’épuisement des cellules souches, à l’accumulation de tissu fibreux et limitent la fonction du muscle. Puisqu’aucun traitement ne s’est révélé efficace lors d’essais cliniques, l’absence de solutions à ce jour pour alléger les symptômes des patients rend la recherche d’approches alternatives essentielle. Nous proposons ici que la stimulation de la régénération est une nouvelle approche qui permet de restaurer et maintenir la fonction du muscle. Cette étude porte sur l’utilisation de l’Apéline-13, un candidat prometteur pour le traitement de la dystrophie musculaire. L’Apéline-13 est un peptide endogène longtemps étudié pour son rôle dans le contrôle du métabolisme et comme régulateur du système cardiovasculaire chez la souris. Récemment, il a été révélé que l’Apéline-13 stimule la fonction des cellules souches musculaires. Nos résultats montrent que le traitement systémique à l’Apéline-13 mobilise les cellules souches musculaires, augmentant grandement la régénération du muscle squelettique, et améliorant drastiquement les performances motrices dans le modèle de Dystrophie Musculaire Congénitale DyW/DyW. De plus, aucun effet secondaire n’a été observé et le traitement a été bien toléré par les souris. Il s’agit de résultats importants, considérant l’absence de traitements efficaces pour la gestion des dystrophies musculaires. L’industrie pharmaceutique connait aussi un intérêt récent pour la recherche dans le domaine des maladies rares. Un composé avec un effet bénéfique sur l’état de santé dans la dystrophie musculaire pourrait avoir un effet drastique sur la vie des patients."],"dc:identifier.uri":["http://hdl.handle.net/11143/20511"],"dc:language.iso":["fr"],"dc:publisher":["Université de Sherbrooke"],"dc:subject":["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"],"dc:title":["Stimulation de la régénération endogène dans le traitement de la dystrophie musculaire"],"dc:type":["Mémoire de maîtrise"],"thesis:degree_discipline":["Pharmacologie"],"thesis:degree_level":["Maîtrise"],"thesis:degree_name":["M. Sc."],"thesis:institution_name":["Faculté de médecine et des sciences de la santé"]},"updated_at":"2026-07-27T21:07:28Z"}