Aptamer Selection for Myostatin to Treat Muscular Dystrophy

Aptamer Selection for Myostatin to Treat Muscular Dystrophy

Leta Ko

September 16, 2011

Fall 2011

N34 RNA- Myostatin

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, which can cause a 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, such as 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. 

Here's a link to my Proposal: http://dl.dropbox.com/u/39652698/Leta%20Ko.docx 
Here's a link to my Progress Report 1: http://dl.dropbox.com/u/39652698/Progress%20Report1.docx 
Here's a link to my Final Manuscript: http://dl.dropbox.com/u/39652698/FINAL..docx

I'm sorry this was a couple of minutes late, but I couldn't figure out the dropbox sharing.