PEGylated Mechano Growth Factor (MGF)

PEGylated Mechano Growth Factor (MGF)

Quick summary: MGF is a splice variant of the IGF produced by a frame shift if the IGF gene. MGF increase the muscle stem cell count, so that more may fuse and become part of adult muscle cells. This is a process required for adult muscle cells to continue growing.

Why PEGylate MGF?
MGF exhibits local effects in skeletal muscle and without modification is not systemic (can’t travel through the body). The problem with synthetic MGF is that it is introduced IM and is water based so it goes into the blood stream. MGF is not stable in the blood stream for more than a matter of minutes. Biologically produced MGF is made locally and does not enter the bloodstream and is short acting so stability is not an issue. By PEGylating the MGF we can make synthetic MGF injected IM almost as efficient as local produced MGF. Clinically proven Advanced Pegylation, the technology of polyethylene glycol (PEG) conjugation, holds significant promise in maintaining effective plasma concentrations of systemically administered drugs. It does this by surrounding part of the peptide with a unique structure made of polyethylene glycol, which can be attached to a protein molecule. The result of a correct PEGylation is simlar to the protective mechanism of a turtle shell. The polyethylene glycol groups protect the peptide but don’t surround it completely. The active sites of the peptide are still free to do their biological function. In this case the shell is a negative charged shield against positively charged compounds that would affect the protein. This also provides a nice steric chamber for the peptide to reside in. So it’s a happy turtle

Neurological research has shown that utilizing PEGylated MGF resulted in a longer more stable acting version of the MGF peptide in serum/blood.

Bottom line
PEGylation can improve performance and dosing convenience of peptides, proteins, antibodies, oligonucleotides and many small molecules by optimizing pharmacokinetics, increasing bioavailability, and decreasing immunogenicity and dosing frequency. PEGylation also can increase therapeutic efficacy by enabling increased drug concentration, improved biodistribution, and longer dwell time at the site of action. As a result, therapeutic drug concentrations can be achieved with less frequent dosing—a significant benefit to patients who are taking injected drugs.

The PEG itself does not react in the body and is very safe. PEG has been approved by the US Food and Drug Administration (FDA) as a base or vehicle for use in foods and cosmetics and in injectable, topical, rectal and nasal pharmaceutical formulations. PEG has demonstrated little toxicity, is eliminated intact by the kidneys or in the feces and lacks immunogenicity. The risk associated with current PEGylated drugs are due to the way the drug itself acts not the PEG. MGF, as it is being currently sold, is getting a bad rep from people due to the fact they feel that they are not seeing gains from it. Many people believe that the use of MGF in their cycles or protocols just flat out won’t work, however, this is far from the truth.
More MGF information

Complete Overview of MGF or IGF-IEc

From its sequence, MGF is derived from the IGF-I gene by alternative splicing and has different 3′ exons to the liver or systemic type (IGF-IEa). It has a 49 base pair insert in the human, and a 52 base pair insert in rodents, within the E domain of exon 5. This insert results in a reading frame shift, with a different carboxy (C) terminal sequence to that of systemic IGF-IEa. MGF and the other IGF isoforms have the same 5′ exons that encode the IGF-I ligand-binding domain. Processing of pro-peptide yields a mature peptide that is involved in upregulating protein synthesis. However, there is evidence that the carboxy-terminal of the MGF peptide also acts as a separate growth factor. This stimulates division of mononucleated myoblasts or satellite (stem) cells, thereby increasing the number available for local repair

During the early stage of skeletal muscle development, myoblasts (muscle stem cells) fuse to form syncytial myotubes, which become innervated and develop into muscle fibres. Thereafter, mitotic proliferation of nuclei within the muscle fibres ceases. However, during postnatal (after development) growth, additional nuclei are provided by satellite cells (myoblast) fusing with myotubules. Muscle damage-recovery seems to have a similar cellular mechanism, in that satellite cells become activated and fuse with the damaged muscle fibres (reviewed by Goldring et al. 2002). This is also pertinent to certain diseases such as muscular dystrophy in which muscle tissue is not maintained and which have been associated with a deficiency in active satellite (stem) cells (Megeney et al. 1996; Seale & Rudnicki, 2000) and in myogenic factors (Heslop et al. 2000). Skeletal muscle mass and regenerative capacity have also been shown to decline with age (Sadeh, 1988; Carlson et al. 2001). The reduced capacity to regenerate in older muscle seems to be due to the decreased ability to activate satellite cell proliferation (Chakravarthy et al. 2000). The markedly lower expression of MGF in older rat muscles (Owino et al. 2001) and human muscle (Hameed et al. 2003) in response to mechanical overload has been associated with the failure to activate satellite cells, leading to age-related muscle loss (Owino et al. 2001). Your muscle cels can not grow once they have reached a certain size unless they obtain more nuclei from the myoblast. MGF increases the myblast available to donate their nuclei to the adult muscle cell.

“MGF appears to have a dual action in that, like the other IGF-I isoforms, it upregulates protein synthesis as well as activating satellite cells. However, the latter role of MGF is probably more important as most of the mature IGF-I will be derived from IGF-IEa during the second phase of repair. Nevertheless, it has been shown that MGF is a potent inducer of muscle hypertrophy in experiments in which the cDNA of MGF was inserted into a plasmid vector and introduced by intramuscular injection. This resulted in a 20 % increase in the weight of the injected muscle within 2 weeks, and the analyses showed that this was due to an increase in the size of the muscle fibres (Goldspink, 2001). Similar experiments by other groups have also been carried out using a viral construct containing the liver type of IGF-I, which resulted in a 25 % increase in muscle mass, but this took over 4 months to develop (Musaro et al. 2001). Hence, the dual role MGF plays in inducing satellite cell activation as well as protein synthesis suggests it is much more potent than the liver type or IGF-IEa for inducing rapid hypertrophy.”

These results are based on actual transplantation of the DNA coding for the peptides. This is a permanent effect and much more potent than IM injections of the peptide itself. You will not see a 20% increase in muscle mass through IM injections as claimed above.

PEGylated MGF dosing Protocols

The PEGylated version is going to be much longer lasting making a 1-2 dose per week procedure possible. I still think its best used with IGF or AAS to maximize the benefits so here are some sample protocols

Once a week PEG MGF/ IGF
Sunday 100-300 mcg MGF you can choose to site inject if you wish. I think splitting large doses may benefit.
Monday –Fri IGF 50mcg e/d

Twice a week PEG MGF / IGF
Sunday and Wed MGF 50-150 mcg
MT, ThF IGF 50 mcg

These protocols are just to start as this is brand new feel free to tweak them if you like. I will update them after we have done some testing.

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