CMT and Neurogenic Disease

Shy, Micheal; Herrmann, DN; Thomas, Florian P.; Quinn, Colin; Statland, Jeffrey; Walk, David; Johnson, Nicholas E.; Subramony, S. H.; Karam, Chafic; Mozaffar, Tahseen; D'Eon, S.; Miller, Barry; Glasser, Chad; Sherman, ML; Attie, Kenneth M.

doi:10.1016/j.nmd.2018.06.387

Cited by 3 publications

(1 citation statement)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our findings complement those of an earlier study 23 and collectively provide a strong rationale for evaluating follistatin-based interventions such as ACE-083 in disorders with focal muscle weakness. ACE-083 promotes focal muscle growth in healthy volunteers 24 and is being evaluated in phase 2 studies as a therapeutic agent for patients with CMT and FSHD 25,26 .…”

Section: Discussionmentioning

confidence: 99%

Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease

Pearsall

Davies

Cannell

et al. 2019

Sci Rep

View full text Add to dashboard Cite

Skeletal muscle is under inhibitory homeostatic regulation by multiple ligands of the transforming growth factor-β (TGFβ) superfamily. Follistatin is a secreted protein that promotes muscle growth and function by sequestering these ligands extracellularly. In the present study, we evaluated the potential of ACE-083 – a locally acting, follistatin-based fusion protein – as a novel therapeutic agent for focal or asymmetric myopathies. Characterization of ACE-083 in vitro revealed its high affinity for heparin and extracellular matrix while surface plasmon resonance and cell-based assays confirmed that ACE-083 binds and potently neutralizes myostatin, activin A, activin B and growth differentiation factor 11 (GDF11). Intramuscular administration of ACE-083 caused localized, dose-dependent hypertrophy of the injected muscle in wild-type mice and mouse models of Charcot-Marie-Tooth disease (CMT) and Duchenne muscular dystrophy, with no evidence of systemic muscle effects or endocrine perturbation. Importantly, ACE-083 also increased the force of isometric contraction in situ by the injected tibialis anterior muscle in wild-type mice and disease models and increased ankle dorsiflexion torque in CMT mice. Our results demonstrate the potential of ACE-083 as a therapeutic agent for patients with CMT, muscular dystrophy and other disorders with focal or asymmetric muscle atrophy or weakness.

show abstract

Section: Discussionmentioning

confidence: 99%

Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease

Pearsall

Davies

Cannell

et al. 2019

Sci Rep

View full text Add to dashboard Cite

show abstract

Principles of the activin receptor signaling pathway and its inhibition

Lodberg

2021

Cytokine & Growth Factor Reviews

View full text Add to dashboard Cite

The Role of TGF-β, Activin and Follistatin in Inflammatory Bowel Disease

Esfahani

Day

2023

Gastrointestinal Disorders

View full text Add to dashboard Cite

Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition predominantly affecting the gastrointestinal (GI) tract. An increasing prevalence of IBD has been observed globally. The pathogenesis of IBD includes a complex interplay between the intestinal microbiome, diet, genetic factors and immune responses. The consequent imbalance of inflammatory mediators ultimately leads to intestinal mucosal damage and defective repair. Growth factors, given their specific roles in maintaining the homeostasis and integrity of the intestinal epithelium, are of particular interest in the setting of IBD. Furthermore, direct targeting of growth factor signalling pathways involved in the regeneration of the damaged epithelium and the regulation of inflammation could be considered as therapeutic options for individuals with IBD. Several members of the transforming growth factor (TGF)-β superfamily, particularly TGF-β, activin and follistatin, are key candidates as they exhibit various roles in inflammatory processes and contribute to maintenance and homeostasis in the GI tract. This article aimed firstly to review the events involved in the pathogenesis of IBD with particular emphasis on TGF-β, activin and follistatin and secondly to outline the potential role of therapeutic manipulation of these pathways.

show abstract

CMT and Neurogenic Disease

Cited by 3 publications

References 0 publications

Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease

Follistatin-based ligand trap ACE-083 induces localized hypertrophy of skeletal muscle with functional improvement in models of neuromuscular disease

Principles of the activin receptor signaling pathway and its inhibition

The Role of TGF-β, Activin and Follistatin in Inflammatory Bowel Disease

Contact Info

Product

Resources

About