Abstract
Since the discovery of the myostatin/ActRIIB signaling pathway 15 years ago, numerous strategies were developed to block its inhibitory function during skeletal muscle growth. Accumulating evidence demonstrates that abrogation of myostatin/ActRIIB signaling ameliorates pathology and function of dystrophic muscle in animal models for Duchenne muscular dystrophy (DMD). Therapeutic trials in healthy man and muscular dystrophy patients suggest feasibility of blockade strategies for potential clinical use. However, many key questions on the effect of myostatin/ActRIIB blockade remain unresolved; such as the underlying molecular mechanism that triggers muscle growth, the effect on muscle regeneration and adult muscle stem cell regulation and whether it causes long term metabolic alterations. Current therapeutic strategies aim to systemically abrogate myostatin/ActRIIB signaling. Although this ensures widespread effect on musculature, it also interferes with ActRIIB signaling in other tissues than skeletal muscle, thereby risking adverse effects. This review discusses current knowledge on myostatin/ActRIIB signaling and its potential value as a therapeutic target for DMD.
Keywords: Activin receptor, duchenne muscular dystrophy, mdx mouse, myostatin, skeletal muscle, myostatin/ActRIIB, DMD, MSTN, mdx, Mstn
Current Gene Therapy
Title:Interference with Myostatin/ActRIIB Signaling as a Therapeutic Strategy for Duchenne Muscular Dystrophy
Volume: 12 Issue: 3
Author(s): Helge Amthor and Willem M.H. Hoogaars
Affiliation:
Keywords: Activin receptor, duchenne muscular dystrophy, mdx mouse, myostatin, skeletal muscle, myostatin/ActRIIB, DMD, MSTN, mdx, Mstn
Abstract: Since the discovery of the myostatin/ActRIIB signaling pathway 15 years ago, numerous strategies were developed to block its inhibitory function during skeletal muscle growth. Accumulating evidence demonstrates that abrogation of myostatin/ActRIIB signaling ameliorates pathology and function of dystrophic muscle in animal models for Duchenne muscular dystrophy (DMD). Therapeutic trials in healthy man and muscular dystrophy patients suggest feasibility of blockade strategies for potential clinical use. However, many key questions on the effect of myostatin/ActRIIB blockade remain unresolved; such as the underlying molecular mechanism that triggers muscle growth, the effect on muscle regeneration and adult muscle stem cell regulation and whether it causes long term metabolic alterations. Current therapeutic strategies aim to systemically abrogate myostatin/ActRIIB signaling. Although this ensures widespread effect on musculature, it also interferes with ActRIIB signaling in other tissues than skeletal muscle, thereby risking adverse effects. This review discusses current knowledge on myostatin/ActRIIB signaling and its potential value as a therapeutic target for DMD.
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Amthor Helge and M.H. Hoogaars Willem, Interference with Myostatin/ActRIIB Signaling as a Therapeutic Strategy for Duchenne Muscular Dystrophy, Current Gene Therapy 2012; 12 (3) . https://dx.doi.org/10.2174/156652312800840577
DOI https://dx.doi.org/10.2174/156652312800840577 |
Print ISSN 1566-5232 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5631 |
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