Glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice

Abstract Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by progressive muscle wasting and weakness and premature death. Glucocorticoids (e.g. prednisolone) remain the only drugs with a favorable impact on DMD patients, but not without side effects. We have demonstrate...

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Autores principales:	Daniel J. Ham, Anastasia Gardner, Tahnee L. Kennedy, Jennifer Trieu, Timur Naim, Annabel Chee, Francesca M. Alves, Marissa K. Caldow, Gordon S. Lynch, René Koopman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6271200ce1974e419391ebe4bea3de4c
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spelling	oai:doaj.org-article:6271200ce1974e419391ebe4bea3de4c2021-12-02T16:08:05ZGlycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice10.1038/s41598-019-49140-x2045-2322https://doaj.org/article/6271200ce1974e419391ebe4bea3de4c2019-09-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-49140-xhttps://doaj.org/toc/2045-2322Abstract Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by progressive muscle wasting and weakness and premature death. Glucocorticoids (e.g. prednisolone) remain the only drugs with a favorable impact on DMD patients, but not without side effects. We have demonstrated that glycine preserves muscle in various wasting models. Since glycine effectively suppresses the activity of pro-inflammatory macrophages, we investigated the potential of glycine treatment to ameliorate the dystrophic pathology. Dystrophic mdx and dystrophin-utrophin null (dko) mice were treated with glycine or L-alanine (amino acid control) for up to 15 weeks and voluntary running distance (a quality of life marker and strong correlate of lifespan in dko mice) and muscle morphology were assessed. Glycine increased voluntary running distance in mdx mice by 90% (P < 0.05) after 2 weeks and by 60% (P < 0.01) in dko mice co-treated with prednisolone over an 8 week treatment period. Glycine treatment attenuated fibrotic deposition in the diaphragm by 28% (P < 0.05) after 10 weeks in mdx mice and by 22% (P < 0.02) after 14 weeks in dko mice. Glycine treatment augmented the prednisolone-induced reduction in fibrosis in diaphragm muscles of dko mice (23%, P < 0.05) after 8 weeks. Our findings provide strong evidence that glycine supplementation may be a safe, simple and effective adjuvant for improving the efficacy of prednisolone treatment and improving the quality of life for DMD patients.Daniel J. HamAnastasia GardnerTahnee L. KennedyJennifer TrieuTimur NaimAnnabel CheeFrancesca M. AlvesMarissa K. CaldowGordon S. LynchRené KoopmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-12 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel J. Ham Anastasia Gardner Tahnee L. Kennedy Jennifer Trieu Timur Naim Annabel Chee Francesca M. Alves Marissa K. Caldow Gordon S. Lynch René Koopman Glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice
description	Abstract Duchenne muscular dystrophy (DMD) is an X-linked genetic disease characterized by progressive muscle wasting and weakness and premature death. Glucocorticoids (e.g. prednisolone) remain the only drugs with a favorable impact on DMD patients, but not without side effects. We have demonstrated that glycine preserves muscle in various wasting models. Since glycine effectively suppresses the activity of pro-inflammatory macrophages, we investigated the potential of glycine treatment to ameliorate the dystrophic pathology. Dystrophic mdx and dystrophin-utrophin null (dko) mice were treated with glycine or L-alanine (amino acid control) for up to 15 weeks and voluntary running distance (a quality of life marker and strong correlate of lifespan in dko mice) and muscle morphology were assessed. Glycine increased voluntary running distance in mdx mice by 90% (P < 0.05) after 2 weeks and by 60% (P < 0.01) in dko mice co-treated with prednisolone over an 8 week treatment period. Glycine treatment attenuated fibrotic deposition in the diaphragm by 28% (P < 0.05) after 10 weeks in mdx mice and by 22% (P < 0.02) after 14 weeks in dko mice. Glycine treatment augmented the prednisolone-induced reduction in fibrosis in diaphragm muscles of dko mice (23%, P < 0.05) after 8 weeks. Our findings provide strong evidence that glycine supplementation may be a safe, simple and effective adjuvant for improving the efficacy of prednisolone treatment and improving the quality of life for DMD patients.
format	article
author	Daniel J. Ham Anastasia Gardner Tahnee L. Kennedy Jennifer Trieu Timur Naim Annabel Chee Francesca M. Alves Marissa K. Caldow Gordon S. Lynch René Koopman
author_facet	Daniel J. Ham Anastasia Gardner Tahnee L. Kennedy Jennifer Trieu Timur Naim Annabel Chee Francesca M. Alves Marissa K. Caldow Gordon S. Lynch René Koopman
author_sort	Daniel J. Ham
title	Glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice
title_short	Glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice
title_full	Glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice
title_fullStr	Glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice
title_full_unstemmed	Glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice
title_sort	glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/6271200ce1974e419391ebe4bea3de4c
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Glycine administration attenuates progression of dystrophic pathology in prednisolone-treated dystrophin/utrophin null mice

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