Aptamer Selection against Myelin Basic Protein for the Promotion of Multiple Sclerosis Treatment

Aptamer Selection against Myelin Basic Protein  for the Promotion of Multiple Sclerosis Treatment

by Matthew Forster
 

            Multiple Sclerosis (MS) is an autoimmune disease in which the body attacks and damages the myelin sheaths that encase nerve cells.  These damaged sheaths then cannot relay the electrical signals passed between neurons in an efficient manner which can then cause effects such as tremors, fainting spells, muscle spasms, and even complete loss of muscle control¹. The tool most often used to diagnose MS is an MRI scan to look for lesions or scarred areas in the white matter and spinal cord areas of the nervous system. Currently there is no cure for multiple sclerosis but there are many medicinal and physical treatments which help control and prevent further progression of the disease.

            Myelin basic protein (MBP) is important in the process of making the myelin sheath casing and is present in many different isomeric forms². The different forms of MBP contribute to diseases that involve the demyelination of neurons because some forms are more readily digestible, which allows for alteration and modification of the structure of MBP². The posttranslational modification of MBP is thought to be the reason for the development of diseases such as multiple sclerosis³. 

Specific Aim 1: Aptamer Selection for Inhibitory Response to MBP

An RNA ligand, or aptamer, target selection against MBP would be an effective therapeutic treatment for multiple sclerosis by using it to bind to and inhibit the membrane signal transduction pathway which produces glial fibrillous proteins in order to stop the posttranslational modification of MBP⁴. This would provide another medicinal treatment to further halt the myelin degradation process of multiple sclerosis. The selection process will use the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) protocol with an N50 RNA pool, Biotinylated MBP and Streptavidin magnetic beads in the filteration process⁵.

The MBP Biotin conjugate is available through EMD Millipore, Upstate brand, catalog number 13-111, molecular weight of 20Kd and costs $209 for 1mg which would cost around $8.26 per round using 4ug. http://www.millipore.com/catalogue/item/13-111?cid=bios-a-bioc-1011-1209-RC

Full proposal and progress report can be found at:
https://www.dropbox.com/s/tq3hrqac86mipia/MBP%20Progress%20Report%201%20Fall%202012.docx

https://www.dropbox.com/s/ne90br92giq7auc/MBP%20Progress%20Report%202%20Fall%202012.docx

https://www.dropbox.com/s/tbv40hw7us1gmlv/MBP%20Progress%20Report%203%20Fall%202012.docx

 

1.     O’Connor, A., Schwid, S.R., Herrmann, D.N., Markman, J.D., Dworkin, R.H., Pain associated with multiple sclerosis: Systematic review and proposed classification. 2008. PAIN. 137: 1,30.96-111.

2.    Boggs, J. Myelin basic protein: a multifunctional protein. 2006. Cellular and Molecular     Life Sciences. 63, 17: 1945-61.

3.      Wood, D.D., Bilbao, J.M., O’Connors, P., Moscarello, M.A. Acute multiple sclerosis is associated with developmentally immature myelin basic protein. 1996. Ann. Neurol. 40:18-24.

4.  Benveniste, E.N. and Benos D.J. TNF-alpha- and IFN-gamma-mediated signal transduction pathways: effects on glial cell gene expression and function. 1995. FASEB J. 9:1577-84.

5.    Ellington, Andrew D. Szostak, Jack W. In vitro selection of RNA molecules that bind specific ligands. 1990. Nature. 346:818-822.