Aptamer Selection for Myostatin to Treat Muscular Dystrophy

Leta Ko - llk422

Muscular dystrophy is a group of genetic diseases that weaken and degenerate muscle function. The main cause of this condition is due to lack of the muscle protein dystrophin. It can cause loss of control over major skeletal muscles. However, myostatin is a negative regulator for skeletal muscle growth and a member of the transforming growth factor-B family, TGF-B, which binds to cell receptors, Activin type II, to inhibit growth and development of the muscles. Usually, myostatin functions are to prevent skeletal muscles from becoming too large in size.
An idea to reverse the conditions of muscular dystrophy would be to inhibit the binding of myostatin to muscle cell receptors. If myostatin is inhibited, the skeletal muscles can grow and develop (Bogdanovich, 2002). This can be done with the use of RNA ligands, or aptamers. Aptamers bind to specific protein targets with high specificity and affinity, which can provide a good approach to therapeutically treat patients with muscular dystrophy. This could also provide as a good substitute to a myostatin inhibitor experimental drug called, stamulumab, which is a human antibody that inhibits myostatin activity.
An aptamer specific to myostatin can lead to a treatment for patients with muscular dystrophy. Although it is not clear if it can inhibit the complete activity of the negative regulator, it can prevent the bonding of the cell receptor and the negative regulator. Thus, the effects of muscular dystrophy can be reversed by the growth of the skeletal muscles (Wagner, 2002). With this experiment, it is possible to find out whether or not myostatin is still active when bound to aptamers.
Specific Aim 1: Selection of RNA aptamers against myostatin
Myostatin inhibits the growth and development of skeletal muscle tissues. Aptamers can be selected against myostatin to prevent this protein from binding to the muscle cell receptors. Instead the myostatin would bind to the highly specific aptamer, leaving the skeletal muscle tissue free to develop bigger (Gonzalez-Cadavid, 1998). Patients with muscular dystrophy and that have been treated with aptamers specific to myostatin could possibly regain muscle mass and function (Bish, 2011).
10 µg of Myostatin can be purchased by the company 3H Biomedical AB, for a price of $270.00. The catalog number is 3HCYT 418. The higher price reflects the shipping time.


Bish, LT., Sleeper, MM., Forbes, SC., et al. (2011). “Long-term systemic myostatin inhibition via liver-targeted gene transfer in golden retriever muscular dystrophy” Human Gene Therapy.

Bogdanovich, S.,  Krag, T., Barton, E., Morris, L., Whittemore, L. (2002). “Functional improvement of dystrophic muscle by myostatin blockade” Letters to Nature. 420: 418-421.

Gonzalez-Cadavid, N., Taylor, W., Yarasheski, K., et all. (1998). “Organization of the human myostatin gene and expression in healthy men and HIV-infected men with muscle wasting” Proceedings of the National Academy of Sciences of the United States of America. 95(25): 14938-14943.

Wagner, K., McPherron, A., Winick, N., Lee, S. (2002). “Loss of myostatin attenuates severity of muscular dystrophy in mdx mice” Annuals of Neurology. 52(6):832-836.


Jessica Beardsley said...

Sounds like an interesting target with many therapeutic possibilties! Best of luck to you.

Cori Booker said...

This is particular target is of special interest to me as i have known a couple of people who have forms of muscular dystrophy. This is a good idea and i think it's going to lead to a really solid proposal, i'm excited for you :)

Cody Grissom said...

Interesting target, Leta! Good luck!