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, 3
represents 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
Full proposal: https://docs.google.com/open?id=0B2m2NTs-hw5MZnFhQm1ZdGZRajg
Progress report 1: https://docs.google.com/open?id=0B2m2NTs-hw5MTWlkckhQQ0tsUG8
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
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>.
1 comment:
Dear Gubeom,
Here are some suggestions:
1. Please add your name to the text, because this will help with searching.
2. please update your ordering info. We order MBP from Millipore:
EMD Millipore
978.715.4321
cat. #: 13-111
Tagged: Biotin
1 mg
$209.00
3. Add the molecular weight & the cost per a round in your ordering section.
4. the last sentence of your 1st paragraph, doesn't really make sense. If you want anti-herpes viral aptamers, then you should really select against herpes viral pariticles (not MBP). Previously
, you mentioned using an anti-MBP aptamer to block post-translational modifications in MBP to decrease MS progression. i like this idea. Please find that reference again or let me know some info about the ref & I'll try to find it.
5. specific aim #1 - identify an aptamer against MBP
6. speicific aim #2 - develop a therapeutic that prevents post-translational modification of MBP
7. consider reworking figure to better fit the abtract w/out the herpes virus applicatoin.
... well, now I can't find your posting. Let me find it & then return to these comments.
Gwen
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