Pegylated Mechano Growth Factor

Potential Benefits of PEG-MGF

• Promotes muscle repair [1-7]
• Speeds up bone repair [8-10]
• Stimulates muscle growth [11-15]
• Prevents heart disease [16-20]
• Protects against stroke [21-23]
• Promotes cognitive health [24-25]

What is Pegylated Mechano Growth Factor (PEG-MGF)?

PEG-MGF is a split variant of insulin-like growth factor-1 (IGF-1). It is present in the muscles, bones, tendons, brain, and heart tissues after an increased load of stress. Its main purpose is to promote faster recovery from muscle damage. For this reason, it is used by athletes and bodybuilders to recover faster and increase their muscle mass.

How PEG-MGF Works?

PEG-MGF modulates muscle inflammation and enhances the regeneration process by improving the recruitment of the white blood cells called macrophages and neutrophils to the site of injury. This in turn promotes muscle growth and repair. PEG-MGF also promotes neurogenesis (formation of new nerve cells or neurons) by increasing the number of neural progenitor cells (cells that transform to create specialized cell types).

Chemical Structure of PEG-MGF

Research on PEG-MGF

Promotes Muscle Repair

The ability of PEG-MGF to promote muscle recovery is backed by a number of studies:

1. A study showed that PEG-MGF alone can enhance muscle repair in patients with age-related sarcopenia (muscle wasting). [1]
2. In rats, PEG-MGF supplementation slowed the progress of muscle wasting due to mechanical-induced disc degeneration. [2]
3. In rats, PEG-MGF treatment improved the healing of the injured Achilles tendon. [3]
4. A study suggested that PEG-MGF might play a role in skeletal muscle regeneration. [4]
5. In mice, PEG-MGF treatment was found to be effective in treating mild skeletal muscle diseases. [5]
6. A study showed that age-related decline in PEG-MGF production was associated with a higher risk of sarcopenia. [6]
7. In adult male mice, MGF was shown to modulate muscle inflammation and improves the recruitment of macrophages and neutrophils to the site of injury. [7]

Speeds up Bone Repair

PEG-MGF has also been shown to accelerate bone regeneration:

1. In rabbits, PEG-MGF treatment resulted in faster bone-healing by regulating the activity of bone-forming cells. [8]
2. In rabbit models, PEG-MGF significantly improved articular cartilage repair. [9]
3. In mice, MGF administration improved the migration of chondrocytes, the cells responsible for cartilage formation, from bones into the cartilage where they are needed. [10]

Stimulates Muscle Growth

Studies have shown that PEG-MGF can help increase muscle mass:

1. A review of several studies showed that PEG-MGF stimulates muscle growth by regulating muscle cell division. [11]
2. A study showed that PEG-MGF promotes muscle growth by activating certain growth factors. [12]
3. In mice, PEG-MGF stimulated muscle formation. [13]
4. In animal models, PEG-MGF was found to be important in the activation, proliferation, and differentiation of muscle cells. [14]
5. In mice, a single intramuscular administration of MGF resulted in a 25% increase in mean muscle fiber size. [15]

Prevents Heart Disease

Studies show that PEG-MGF can help protect against cardiovascular disease:

1. In sheeps, PEG-MGF protected the heart muscle from ischemia (reduced blood supply) and improved heart function after a heart attack. [16]
2. A study reported that PEG-MGF can help lower the risk of heart disease by preventing programmed cell death of heart muscle cells. [17]
3. PEG-MGF has also been shown to regulate the migration and proliferation of stem cells in the heart. [18]
4. A study found that PEG-MGF plays an integral role in the growth and formation of human heart tissues. [19]
5. In rats, localized delivery of PEG-MGF improved cardiac function following heart attack. [20]

Protects against Stroke

Evidence found that PEG-MGF offers protection against stroke:

1. A study showed that PEG-MGF can help protect against nerve damage due to inadequate blood supply to the brain. [21]
2. Studies also found that PEG-MGF can help prevent stroke by preventing programmed cell death of brain cells in response to oxidative stress. [22-23]

Promotes Cognitive Health

1. In mice, MGF was shown to be effective in reducing the effects of age-related neuron degeneration. [24]
2. In a gerbil model of transient brain ischemia, MGF offered protective effects against the loss of motor-neurons. [25]

Associated Side Effects of PEG-MGF

PEG-MGF side effects are very uncommon. There have been some side effects associated with the use of this drug wherein the patient had one of the issues listed below at some point while being on PEG-MGF. However, these side effects weren’t confirmed to be associated with the treatment and could have been a coincidence and not related to the use of PEG-MGF. Despite this, it was listed as a side effect associated with PEG-MGF even though these associated side effects are very uncommon.

Side effects associated with PEG-MGF may include the following:

• Blood pressure drop
• Hypoglycemia (low blood sugar levels)
• Irregular heart rate
• Swelling of the extremities

References

1. Kandalla PK, Goldspink G, Butler-Browne G, Mouly V. Mechano Growth Factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages. Mech Ageing Dev. 2011 Apr;132(4):154-62. doi: 10.1016/j.mad.2011.02.007. Epub 2011 Feb 25. PMID: 21354439.
2. Xu Q, Fang H, Zhao L, Zhang C, Zhang L, Tian B. Mechano growth factor attenuates mechanical overload-induced nucleus pulposus cell apoptosis through inhibiting the p38 MAPK pathway. Biosci Rep. 2019;39(3):BSR20182462. Published 2019 Mar 28. doi:10.1042/BSR20182462.
3. Zhang B, Luo Q, Kuang D, Ju Y, Song G. Mechano-growth factor E peptide promotes healing of rat injured tendon. Biotechnol Lett. 2016 Oct;38(10):1817-25. doi: 10.1007/s10529-016-2162-8. Epub 2016 Jun 22. PMID: 27334712.
4. Philippou A, Papageorgiou E, Bogdanis G, Halapas A, Sourla A, Maridaki M, Pissimissis N, Koutsilieris M. Expression of IGF-1 isoforms after exercise-induced muscle damage in humans: characterization of the MGF E peptide actions in vitro. In Vivo. 2009 Jul-Aug;23(4):567-75. PMID: 19567392.
5. Gehrig SM, van der Poel C, Hoeflich A, Naim T, Lynch GS, Metzger F. Therapeutic potential of PEGylated insulin-like growth factor I for skeletal muscle disease evaluated in two murine models of muscular dystrophy. Growth Horm IGF Res. 2012 Apr;22(2):69-75. doi: 10.1016/j.ghir.2012.02.004. Epub 2012 Mar 15. PMID: 22424862.
6. Goldspink G, Harridge SD. Growth factors and muscle ageing. Exp Gerontol. 2004 Oct;39(10):1433-8. doi: 10.1016/j.exger.2004.08.010. PMID: 15501012.
7. Sun KT, Cheung KK, Au SWN, Yeung SS, Yeung EW. Overexpression of Mechano-Growth Factor Modulates Inflammatory Cytokine Expression and Macrophage Resolution in Skeletal Muscle Injury. Front Physiol. 2018 Jul 26;9:999. doi: 10.3389/fphys.2018.00999. PMID: 30140235; PMCID: PMC6094977.
8. Deng M, Zhang B, Wang K, et al. Mechano growth factor E peptide promotes osteoblasts proliferation and bone-defect healing in rabbits. Int Orthop. 2011;35(7):1099-1106. doi:10.1007/s00264-010-1141-2.
9. Luo Z, Jiang L, Xu Y, Li H, Xu W, Wu S, Wang Y, Tang Z, Lv Y, Yang L. Mechano growth factor (MGF) and transforming growth factor (TGF)-β3 functionalized silk scaffolds enhance articular hyaline cartilage regeneration in rabbit model. Biomaterials. 2015 Jun;52:463-75. doi: 10.1016/j.biomaterials.2015.01.001. Epub 2015 Mar 18. PMID: 25818452.
10. Jing X, Ye Y, Bao Y, Zhang J, Huang J, Wang R, Guo J, Guo F. Mechano-growth factor protects against mechanical overload induced damage and promotes migration of growth plate chondrocytes through RhoA/YAP pathway. Exp Cell Res. 2018 May 15;366(2):81-91. doi: 10.1016/j.yexcr.2018.02.021. Epub 2018 Feb 20. PMID: 29470961.
11. Matheny RW Jr, Nindl BC, Adamo ML. Minireview: Mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration. Endocrinology. 2010;151(3):865-875. doi:10.1210/en.2009-1217.
12. Potency of Full- Length MGF to Induce Maximal Activation of the IGF-I R Is Similar to Recombinant Human IGF-I at High Equimolar Concentrations. Joseph A. M. J. L. Janssen ,Leo J. Hofland,Christian J. Strasburger,Elisabeth S. R. van den Dungen,Mario Thevis Published: March 18, 2016https://doi.org/10.1371/journal.pone.0150453.
13. Chikazawa M, Shimizu M, Yamauchi Y, Sato R. Bridging molecules are secreted from the skeletal muscle and potentially regulate muscle differentiation. Biochem Biophys Res Commun. 2020 Jan 29;522(1):113-120. doi: 10.1016/j.bbrc.2019.11.010. Epub 2019 Nov 18. PMID: 31753488.
14. Harridge SD. Ageing and local growth factors in muscle. Scand J Med Sci Sports. 2003 Feb;13(1):34-9. doi: 10.1034/j.1600-0838.2003.20235.x. PMID: 12535315.
15. Goldspink GResearch on mechano growth factor: its potential for optimising physical training as well as misuse in dopingBritish Journal of Sports Medicine 2005;39:787-788.
16. Carpenter V, Matthews K, Devlin G, Stuart S, Jensen J, Conaglen J, Jeanplong F, Goldspink P, Yang SY, Goldspink G, Bass J, McMahon C. Mechano-growth factor reduces loss of cardiac function in acute myocardial infarction. Heart Lung Circ. 2008 Feb;17(1):33-9. doi: 10.1016/j.hlc.2007.04.013. Epub 2007 Jun 19. PMID: 17581790.
17. Doroudian G, Pinney J, Ayala P, Los T, Desai TA, Russell B. Sustained delivery of MGF peptide from microrods attracts stem cells and reduces apoptosis of myocytes. Biomed Microdevices. 2014;16(5):705-715. doi:10.1007/s10544-014-9875-z.
18. Collins J. M., Goldspink P. H., Russell B. (2010). Migration and proliferation of human mesenchymal stem cells is stimulated by different regions of the mechano-growth factor prohormone. J. Mol. Cell. Cardiol. 49, 1042–1045 10.1016/j.yjmcc.2010.09.017.
19. Deng M., Wang Y., Zhang B., Liu P., Xiao H., Zhao J. (2012). New proangiogenic activity on vascular endothelial cells for C-terminal mechano growth factor. Acta Biochim. Biophys. Sin. (Shanghai) 44, 316–322 10.1093/abbs/gms012.
20. Peña JR, Pinney JR, Ayala P, Desai TA, Goldspink PH. Localized delivery of mechano-growth factor E-domain peptide via polymeric microstructures improves cardiac function following myocardial infarction. Biomaterials. 2015 Apr;46:26-34. doi: 10.1016/j.biomaterials.2014.12.050. Epub 2015 Jan 16. PMID: 25678113; PMCID: PMC4328136.
21. A strong neuroprotective effect of the autonomous C‐terminal peptide of IGF‐1 Ec (MGF) in brain ischemia Joanna Dłużniewska Anna Sarnowska  Małgorzata Beręsewicz  Ian Johnson  Surjit K. S. Srai Bala Ramesh  Geoffrey Goldspink  Dariusz C. Górecki  Barbara Zabłocka First published: 06 September 2005 https://doi.org/10.1096/fj.05-3786fje.
22. Dluzniewska J, Sarnowska A, Beresewicz M, Johnsomn I, Srai SK, Ramesh B, Goldspink G, Gorecki DC, Zablocka B. A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia. FASEB J. 2005;19:1896–8.
23. Quesada A, Ogi J, Schultz J, Handforth A. C-terminal mechano-growth factor induces heme oxygenase-1-mediated neuroprotection of SH-SY5Y cells via the protein kinase Cε/Nrf2 pathway. J Neurosci Res. 2011;89:394–405.
24. Available from https://blogs.biomedcentral.com/on-biology/2017/07/20/hearts-minds-mice-men-mechano-growth-factor-new-tool-battle-age-related-neuron-loss/.
25. Dluzniewska J, Sarnowska A, Beresewicz M, Johnson I, Srai SK, Ramesh B, Goldspink G, Górecki DC, Zabłocka B. A strong neuroprotective effect of the autonomous C-terminal peptide of IGF-1 Ec (MGF) in brain ischemia. FASEB J. 2005 Nov;19(13):1896-8. doi: 10.1096/fj.05-3786fje. Epub 2005 Sep 6. PMID: 16144956.