Current and emerging treatment strategies for Duchenne muscular dystrophy

Jean K Mah Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Abstract: Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to...

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Autor principal:	Mah JK
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2016
Materias:	Duchenne muscular dystrophy emerging treatment standard of care review Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
Acceso en línea:	https://doaj.org/article/846ed0159e774cbbaf83fcb801b3cb14
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spelling	oai:doaj.org-article:846ed0159e774cbbaf83fcb801b3cb142021-12-02T03:19:51ZCurrent and emerging treatment strategies for Duchenne muscular dystrophy1178-2021https://doaj.org/article/846ed0159e774cbbaf83fcb801b3cb142016-07-01T00:00:00Zhttps://www.dovepress.com/current-and-emerging-treatment-strategies-for-duchenne-muscular-dystro-peer-reviewed-article-NDThttps://doaj.org/toc/1178-2021Jean K Mah Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Abstract: Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying mutations using new gene-editing technologies and corticosteroid analogs with better safety profiles offers renewed hope for many individuals with DMD and their families. Keywords: Duchenne muscular dystrophy, emerging treatment, standard of care, review Mah JKDove Medical PressarticleDuchenne muscular dystrophyemerging treatmentstandard of carereviewNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571Neurology. Diseases of the nervous systemRC346-429ENNeuropsychiatric Disease and Treatment, Vol 2016, Iss Issue 1, Pp 1795-1807 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Duchenne muscular dystrophy emerging treatment standard of care review Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429
spellingShingle	Duchenne muscular dystrophy emerging treatment standard of care review Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Neurology. Diseases of the nervous system RC346-429 Mah JK Current and emerging treatment strategies for Duchenne muscular dystrophy
description	Jean K Mah Department of Pediatrics and Clinical Neurosciences, Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada Abstract: Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMD gene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMD mutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying mutations using new gene-editing technologies and corticosteroid analogs with better safety profiles offers renewed hope for many individuals with DMD and their families. Keywords: Duchenne muscular dystrophy, emerging treatment, standard of care, review
format	article
author	Mah JK
author_facet	Mah JK
author_sort	Mah JK
title	Current and emerging treatment strategies for Duchenne muscular dystrophy
title_short	Current and emerging treatment strategies for Duchenne muscular dystrophy
title_full	Current and emerging treatment strategies for Duchenne muscular dystrophy
title_fullStr	Current and emerging treatment strategies for Duchenne muscular dystrophy
title_full_unstemmed	Current and emerging treatment strategies for Duchenne muscular dystrophy
title_sort	current and emerging treatment strategies for duchenne muscular dystrophy
publisher	Dove Medical Press
publishDate	2016
url	https://doaj.org/article/846ed0159e774cbbaf83fcb801b3cb14
work_keys_str_mv	AT mahjk currentandemergingtreatmentstrategiesforduchennemusculardystrophy
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Current and emerging treatment strategies for Duchenne muscular dystrophy

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