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.
Export Options
About this article
Cite this article as:
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 |
Call for Papers in Thematic Issues
Programmed Cell Death Genes in Oncology: Pioneering Therapeutic and Diagnostic Frontiers (BMS-CGT-2024-HT-45)
Programmed Cell Death (PCD) is recognized as a pivotal biological mechanism with far-reaching effects in the realm of cancer therapy. This complex process encompasses a variety of cell death modalities, including apoptosis, autophagic cell death, pyroptosis, and ferroptosis, each of which contributes to the intricate landscape of cancer development and ...read more
Related Journals
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Stroke in Women - Oral Contraception, Pregnancy, and Hormone Replacement Therapy
Current Vascular Pharmacology Metabolic Profiling in Disease Diagnosis, Toxicology and Personalized Healthcare
Current Pharmaceutical Biotechnology LNA Antisense: A Review
Current Physical Chemistry Role of Biotransformation in Conceptal Toxicity of Drugs and Other Chemicals
Current Pharmaceutical Design A Comprehensive Review on Hydrogels
Current Drug Delivery Update to Medicinal Chemistry of Nicotinamide in the Treatment of Ischemia and Reperfusion
Medicinal Chemistry Reviews - Online (Discontinued) Type 2 Diabetes and its Impact on the Immune System
Current Diabetes Reviews The Therapeutic Potential of Rutin for Diabetes: An Update
Mini-Reviews in Medicinal Chemistry Pharmacogenetics of Target Genes Across Doxorubicin Disposition Pathway: A Review
Current Drug Metabolism Dietary Approaches and Alternative Therapies for Rheumatoid Arthritis
Current Nutrition & Food Science MmpL3 Inhibitors: Diverse Chemical Scaffolds Inhibit the Same Target
Mini-Reviews in Medicinal Chemistry Cellular Cardiomyoplasty – Challenges of a New Era
Current Tissue Engineering (Discontinued) Hypothermia and Alzheimer's Disease Neuropathogenic Pathways
Current Alzheimer Research The Effect of Chemotherapy/Radiotherapy on Cancerous Pattern Recognition by NK Cells
Current Medicinal Chemistry The Addiction Potential of Hyperpalatable Foods
Current Drug Abuse Reviews The Role of Inflammation in Epicardial Adipose Tissue in Heart Diseases
Current Pharmaceutical Design Ductal Carcinoma In Situ: Clinical Trials Update and Resolving Controversies
Current Cancer Therapy Reviews Recent Advances in Neuro-Endocrine-Immune Interactions in the Pathophysiology of Rheumatoid Arthritis
Current Rheumatology Reviews Emerging Roles for Modulation of microRNA Signatures in Cancer Chemoprevention
Current Cancer Drug Targets Germline Genetics of the p53 Pathway Affect Longevity in a Gender Specific Manner
Current Aging Science