Follistatin 344

[01dragonslayer]

Follistatin 344 (and 315)



Follistatin, also called activin-binding protein, is found in nearly all tissues of vertebrate animals. Its primary function is to neutralize members of the TGF-β family, which play fundamental roles in everything from growth and development to energy homeostasis and immune system regulation. In particular, follistatin interacts with activin, which plays an important part in cell proliferation and cell death as well as in the immune response as it applies to wound repair1,2.

Follistatin 344 and Follistatin 315 are engineered analogues of naturally occurring follistatin. Both are created by alternative splicing of the follistatin mRNA transcript. Scientific research in non-human primates as well as in mice have indicated that both molecules are capable of improving muscle growth by antagonizing myostatin (a member of the TGF-β family).

Follistatin 344 Research Studies

The first evidence that follistatin could enhance muscle growth came from studies conducted in mice in 2001. These studies found that myostatin, a known negative regulator of skeletal muscle growth, interacted with activin type II receptors found on muscle cells. Follistatin 344 interacts with these same receptors and is a competitive antagonist to myostatin. By blocking myostatin’s ability to bind to the activin receptors on muscle cells, follistatin 344 can allow for massive increases in muscle mass3.

Scientists are speculating on a number of ways that follistatin may be put to clinical use for muscle growth in the future. Research in mice from 2009 has indicated that follistatin might be useful in the disease spinal muscular atrophy (SMA). In SMA, there is a loss of function mutation that causes death of spinal motor neurons. When these nerves die, the muscles that they connect to atrophy as well. Research shows that follistatin not only preserves muscle tissue in mice with SMA, but that it also helps to preserve spinal motor neurons by creating a positive feedback loop. In fact, the mice in the study group lived 30% longer than mice who were not given Follistatin because of enhanced muscle and nerve cell survival4.

Another way in which the muscle-building benefits of follistatin may be put to good use in the future is in the treatment of muscular dystrophy and inclusion body myositis. In both diseases, muscle wasting leaves people too frail to walk or even breathe on their own. Even modest improvements in muscle mass and function would be life-changing for those suffering from these diseases5,6.

Follistatin in the Future

To date, most follistatin research studies have been conducted in animal models. With the successes mentioned above, however, several clinical trials in humans have begun. The topics of new research interest include cardiovascular disease, Becker muscular dystrophy, Duchenne muscular dystrophy, polycystic ovarian syndrome, delayed puberty, and prostate cancer.

The peptide is being investigated not just for its muscle-building properties, but for its anti-cancer properties and its ability to help regulate sexual maturation in children with precocious puberty. Two of the studies have been completed, but the rest are still pending. So far, serious adverse effects have not been noted, but the compound is still in the early stages of the clinical trial process7. With luck, further clinical trials and research will demonstrate that follistatin is safe and it may in the future either become a pharmaceutical itself or serve as the prototype for developing an entire category of new developmental drugs.

Resources

1. Sulyok, S., Wankell, M., Alzheimer, C. & Werner, S. Activin: an important regulator of wound repair, fibrosis, and neuroprotection. Mol. Cell. Endocrinol. 225, 127–132 (2004).

2. Chen, Y.-G. et al. Activin signaling and its role in regulation of cell proliferation, apoptosis, and carcinogenesis. Exp. Biol. Med. Maywood NJ 231, 534–544 (2006).

3. Lee, S. J. & McPherron, A. C. Regulation of myostatin activity and muscle growth. Proc. Natl. Acad. Sci. U. S. A. 98, 9306–9311 (2001).

4. Rose, F. F., Mattis, V. B., Rindt, H. & Lorson, C. L. Delivery of recombinant follistatin lessens disease severity in a mouse model of spinal muscular atrophy. Hum. Mol. Genet. 18, 997–1005 (2009).

5. Success Boosting Monkey Muscle Could Help Humans. NPR.org Available at: http://www.npr.org/templates/story/story.php?storyId=120316010.

6. Kota, J. et al. Follistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates. Sci. Transl. Med. 1, 6ra15 (2009).

7. Follistatin Trials. Available at: https://clinicaltrials.gov/ct2/results?term=follistatin.