Nucleic Acid Aptamer selection against myelin basic protein.

Searching for a MS treatment therapeutic by selecting an aptamer against myelin basic protein

Abstract

            Myelin basic protein (MBP), in simple terms, is a main component of the myelin sheath surrounding axons in the nervous system. Myelin, or myelin sheath, is the white fatty substance that forms a sheath about the central nervous system and certain nerve fibers.¹ The myelin sheath is a covering of axon in nerve cells that allows faster conduction of electrical impulses in nerve system. If the sheath is somehow damaged by autoimmune disease or an infection, the speed of electrical propagation slows down dramatically and individuals may experience a difficulty of controlling certain body parts or even a loss of control. In an autoimmune disease such as multiple sclerosis where myelin sheath is attacked by antibodies, victims experience ascending paralysis and cognitive disability.² MBP, a monomer of about 304 amino acids and varying sizes from 14 to 21kD, ³represents about 30% of the total myelin protein and is an integral structural constituent of the myelin sheath.¹

There has been considerable interest in MBP and its relationship with demyelinating disease. Abnormal amounts of MBP can be detected in the cerebrospinal fluid of individuals with demyelinating disease and in the serum of patients having suffered head injury, leading to a theory that MBP is a response to heal the damaged axon.¹ It was also found that the possible cause of demyelination disease, such as MS, may be the post-translational modification of MBP. In a study where MBPs were isolated from normal and MS human white matter and compared, it was found that MBP from MS patients were missing phosphorylated peptides and increased methylation.^{4, 5.}

 My specific aim (1) is to select an aptamer against MPB and develop a therapeutic that prevents post-translational modification of MBP which seems to a cause of demyelination disease such as MS.

MBP can be purchased from EMD Millipore (Catalog number 13-111). Since the target (BMP) is tagged with biotin, we can use streptavidin beads that form strong covalent bonds. It’s $209.00 per 1 mg. Per round, it will cost $ 8.26 , assuming  each round will use 4 ug. The cost may go down as selecting round advances and conditions become more stringent. The company’s phone number is 978-715-4321.

Gubeom Nam.

Full proposal: https://docs.google.com/open?id=0B2m2NTs-hw5MZnFhQm1ZdGZRajg

Progress report 1: https://docs.google.com/open?id=0B2m2NTs-hw5MTWlkckhQQ0tsUG8

Progress report 2:https://docs.google.com/open?id=0B2m2NTs-hw5MaGswb05qcGJ1ZmM

Final Report https://docs.google.com/file/d/0B2m2NTs-hw5MY0RPY0hlWUJ3LXM/edit

Reference:

      1.     http://www.sigmaaldrich.com/etc/medialib/docs/Sigma/Product_Information_Sheet/2/m1891pis.Par.0001.File.tmp/m1891pis.pdf
      2. "Myelin Function." THE MEDICAL NEWS. Creative Commons Attribution-ShareAlike License. Web. 03 May 2012. <http://www.news-medical.net/health/Myelin-Function.aspx

     3.     "Antibody to Myelin Basic Protein by EnCor Biotechnology Inc." EnCor Biotechnology Inc., Manufacturer of Monoclonal and Polyclonal Antibodies for Cell Biological, Protein Chemical and Biomarker Research. Encor Biotechnology Inc. Web. 04 May 2012.

       4.     "Multiple Sclerosis - An Important Role for Post-Translational Modifications of Myelin Basic Protein in Pathogenesis." Www.mcponline.org. Molecular and Cellular Proteomics, 25 June 2003. Web. 21 Sept. 2012. <http://www.mcponline.org/content/2/7/453.long>.

Wood, D. D., MD, M. A. Moscarello, MD, and J. M. Bilbao, MD. "Acute Multiple Sclerosis (marburg Type) Is Associated with Developmentally Immature Myelin Basic Protein." Onlinelibrary.wiley.com. N.p., 8 Oct. 2004. Web. 21 Sept. 2012. <http://onlinelibrary.wiley.com/doi/10.1002/ana.410400106/abstract
5. Wood, D. D., MD, M. A. Moscarello, MD, and J. M. Bilbao, MD. "Acute Multiple Sclerosis (marburg Type) Is Associated with Developmentally Immature Myelin Basic Protein." Onlinelibrary.wiley.com. N.p., 8 Oct. 2004. Web. 21 Sept. 2012. <http://onlinelibrary.wiley.com/doi/10.1002/ana.410400106/abstract>.