Overview
Following intramuscular or subcutaneous administration, the Ec peptide fragment is rapidly cleaved from the IGF-1 domain by local proteases. The Ec peptide (MGF peptide per se) acts locally via non-IGF-1R mechanisms to upregulate satellite cell mitotic activity. Concurrently, the liberated IGF-1 domain activates IGF-1R on myofibers and myoblasts, initiating canonical anabolic signaling. Systemic exposure is limited due to rapid proteolytic degradation. PEGylated-MGF has demonstrated prolonged half-life (~72+ hours in animal models) with sustained satellite cell activation and reduced injection frequency requirements.
Proposed mechanism
Upon mechanical overload or tissue damage, the IGF-1 gene is alternatively spliced to produce MGF, which contains a unique E-domain peptide sequence (the Ec peptide) not found in systemic IGF-1. MGF's Ec peptide activates quiescent muscle satellite cells, promoting their proliferation before they fuse with existing muscle fibers or form new ones. Separately, the IGF-1 portion of MGF can bind IGF-1 receptors and activate PI3K/Akt and MAPK/ERK signaling cascades to drive protein synthesis and suppress apoptosis.
What the evidence supports
Most data comes from preclinical animal studies. Human clinical trial evidence is limited or absent.
Graded Animal
Evidence drawn from in vivo animal models or in vitro systems. Mechanistically informative; translation to humans is unproven.
Key citations
Representative primary sources, including results that did not favour the compound.
- [1]
Mechano Growth Factor: a tissue-specific anabolic and repair factor
· Annals of the New York Academy of Sciences; Goldspink G, doi: 10.1196/annals.1392.011 · 2007
- [2]
Alternatively spliced mechano growth factor (MGF) propeptide changes localization according to stress to regulate the activity of the IGF-1 receptor in skeletal muscle
· Journal of Cell Science; Dluzniewska J et al. · 2011
- [3]
PEGylation of mechano growth factor affects its nuclear import in myoblasts
· Journal of Cachexia, Sarcopenia and Muscle; Yang SY et al. · 2009
- [4]
Muscle fiber type-specific satellite cell activation and proliferation in response to mechanical overload
· Journal of Applied Physiology · 2005
Citation records in this build are illustrative placeholders for the design.
Reference information for research purposes. Not medical advice, and not a recommendation to use any compound. Many entries describe substances that are not approved for human use.