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The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle

Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were ini...

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Autores principales: Rybalka, Emma, Timpani, Cara A., Debruin, Danielle A., Bagaric, Ryan M., Campelj, Dean G., Hayes, Alan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764137/
https://www.ncbi.nlm.nih.gov/pubmed/33322031
http://dx.doi.org/10.3390/cells9122657
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author Rybalka, Emma
Timpani, Cara A.
Debruin, Danielle A.
Bagaric, Ryan M.
Campelj, Dean G.
Hayes, Alan
author_facet Rybalka, Emma
Timpani, Cara A.
Debruin, Danielle A.
Bagaric, Ryan M.
Campelj, Dean G.
Hayes, Alan
author_sort Rybalka, Emma
collection PubMed
description Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies. All failed to show modification of disease course as dictated by the primary and secondary outcome measures selected: the myostatin inhibition story, thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models have failed to translate into clinical benefit to patients have been purported. However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD.
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spelling pubmed-77641372020-12-27 The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle Rybalka, Emma Timpani, Cara A. Debruin, Danielle A. Bagaric, Ryan M. Campelj, Dean G. Hayes, Alan Cells Perspective Myostatin inhibition therapy has held much promise for the treatment of muscle wasting disorders. This is particularly true for the fatal myopathy, Duchenne Muscular Dystrophy (DMD). Following on from promising pre-clinical data in dystrophin-deficient mice and dogs, several clinical trials were initiated in DMD patients using different modality myostatin inhibition therapies. All failed to show modification of disease course as dictated by the primary and secondary outcome measures selected: the myostatin inhibition story, thus far, is a failed clinical story. These trials have recently been extensively reviewed and reasons why pre-clinical data collected in animal models have failed to translate into clinical benefit to patients have been purported. However, the biological mechanisms underlying translational failure need to be examined to ensure future myostatin inhibitor development endeavors do not meet with the same fate. Here, we explore the biology which could explain the failed translation of myostatin inhibitors in the treatment of DMD. MDPI 2020-12-10 /pmc/articles/PMC7764137/ /pubmed/33322031 http://dx.doi.org/10.3390/cells9122657 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Perspective
Rybalka, Emma
Timpani, Cara A.
Debruin, Danielle A.
Bagaric, Ryan M.
Campelj, Dean G.
Hayes, Alan
The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle
title The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle
title_full The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle
title_fullStr The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle
title_full_unstemmed The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle
title_short The Failed Clinical Story of Myostatin Inhibitors against Duchenne Muscular Dystrophy: Exploring the Biology behind the Battle
title_sort failed clinical story of myostatin inhibitors against duchenne muscular dystrophy: exploring the biology behind the battle
topic Perspective
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7764137/
https://www.ncbi.nlm.nih.gov/pubmed/33322031
http://dx.doi.org/10.3390/cells9122657
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