Journal ArticleDOI
Myostatin inhibitor ACE-031 treatment of ambulatory boys with Duchenne muscular dystrophy: Results of a randomized, placebo-controlled clinical trial
Craig Campbell,Hugh J. McMillan,Jean K. Mah,Mark A. Tarnopolsky,Kathryn Selby,Ty McClure,Dawn Wilson,Matthew L. Sherman,Diana M. Escolar,Kenneth M. Attie +9 more
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TLDR
ACE‐031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT and myostatin inhibition is a promising therapeutic approach for DMD.Abstract:
Introduction: ACE-031 is a fusion protein of activin receptor type IIB and IgG1-Fc, which binds myostatin and related ligands. It aims to disrupt the inhibitory effect on muscle development and provide potential therapy for myopathies like Duchenne muscular dystrophy (DMD). Methods: ACE-031 was administered subcutaneously every 2–4 weeks to DMD boys in a randomized, double-blind, placebo-controlled, ascending-dose trial. The primary objective was safety evaluation. Secondary objectives included characterization of pharmacokinetics and pharmacodynamics. Results: ACE-031 was not associated with serious or severe adverse events. The study was stopped after the second dosing regimen due to potential safety concerns of epistaxis and telangiectasias. A trend for maintenance of the 6-minute walk test (6MWT) distance in the ACE-031 groups compared with a decline in the placebo group (not statistically significant) was noted, as was a trend for increased lean body mass and bone mineral density (BMD) and reduced fat mass. Conclusion: ACE-031 use demonstrated trends for pharmacodynamic effects on lean mass, fat mass, BMD, and 6MWT. Non–muscle-related adverse events contributed to the decision to discontinue the study. Myostatin inhibition is a promising therapeutic approach for DMD. Muscle Nerve 55: 458–464, 2017read more
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Targeting TGF-β Mediated SMAD Signaling for the Prevention of Fibrosis
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Duchenne muscular dystrophy.
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Therapeutic developments for Duchenne muscular dystrophy.
TL;DR: This Review outlines important developments in these research areas and specifically focuses on new therapies that are in the clinical trial phase or have already been approved for Duchenne muscular dystrophy.
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A review of sarcopenia: Enhancing awareness of an increasingly prevalent disease
TL;DR: Resistance training and nutritional supplementation are the primary methods for treating sarcopenia and trials with various agents, including selective androgen receptor modulators and myostatin inhibitors show promise as future treatment options.
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Clinical relevance of sarcopenia in chronic kidney disease.
Ranjani N. Moorthi,Keith G. Avin +1 more
TL;DR: Sarcopenia, now with its own International Classification of Diseases, 10th Revision (ICD-10) code, is of importance clinically and should be accounted for in research studies in patients with CKD.
References
More filters
Journal ArticleDOI
Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member.
TL;DR: Results suggest that GDF-8 functions specifically as a negative regulator of skeletal muscle growth, which is significantly larger than wild-type animals and show a large and widespread increase in skeletal muscle mass.
Journal ArticleDOI
Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management
Katharine Bushby,Richard S. Finkel,David J. Birnkrant,Laura E. Case,Paula R. Clemens,Linda H. Cripe,Ajay Kaul,Kathi Kinnett,Craig M. McDonald,Shree Pandya,James Poysky,Frederic Shapiro,Jean Tomezsko,Carolyn M. Constantin +13 more
TL;DR: These recommendations provide a framework for recognising the multisystem primary manifestations and secondary complications of DMD and for providing coordinated multidisciplinary care.
Journal ArticleDOI
Regulation of myostatin activity and muscle growth
TL;DR: The findings suggest that the propeptide, follistatin, or other molecules that block signaling through this pathway may be useful agents for enhancing muscle growth for both human therapeutic and agricultural applications.
Journal ArticleDOI
A deletion in the bovine myostatin gene causes the double-muscled phenotype in cattle.
Luc Grobet,Luis José Royo Martin,Dominique Poncelet,Dimitri Pirottin,Benoît Brouwers,Juliette Riquet,Andreina Schoeberlein,S. Dunner,François Ménissier,Julio Massabanda,Ruedi Fries,R. Hanset,Michel Georges +12 more
TL;DR: It is demonstrated that a mutation in bovine MSTN, which encodes myostatin, a member of the TGFβ superfamily, is responsible for the double-muscled phenotype, and an 11-bp deletion in the coding sequence for the bioactive carboxy-termihal domain of the protein causing the muscular hypertrophy observed in Belgian Blue cattle is reported.
Journal ArticleDOI
Population frequencies of inherited neuromuscular diseases—A world survey
TL;DR: A survey of the world literature of the population frequencies of various inherited neuromuscular diseases has been carried out, with a conservative estimate of the overall prevalence among both sexes around 286 x 10(-6).
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