Selection
of Aptamer Against Myelin Basic Protein for the Promotion of Remyelination
Evan Roberts
Myelin
basic protein (MPB) is a protein found in the central nervous system (CNS) of
many species. MBP is responsible for the adhesion of cytosolic surfaces of multilayered
compact myelin in the CNS and is essential for the formation of CNS myelin. The
demyelinating disease multiple sclerosis (MS) occurs when an immune response is
caused due to presence of myelin (J.M. Boggs, 2006). There is absence of
treatment that prevents progression or induces repair to the myelin in the
human body (Nastasijevic, 2012).
Recently
it has been shown that a single stranded DNA aptamer 40-nucleotides long
selected for affinity to murine myelin shows the property of remyelination (Smestad,
2013). Because this aptamer binds to many mice components of myelin such as
MBP, it is reasonable to believe that an aptamer selected against bovine MBP
could have the same properties and may also bind with human MBP. This aptamer
selected for MBP could provide a base for the creation of a therapeutic for
humans with MS.
Specific
Aim 1: Selection of RNA aptamer against MBP.
An
aptamer selected against mice MBP recently promoted remyelination in a study
done with mice. The myelin-specific aptamer induced remyelination in 35% of the
experimental CNS lesions, compared to 4% and 9% remyelination that took place
in the negative control mice treated with other aptamers (Nastasijevic, 2012).
This study provides evidence that an aptamer selected against MBP can provide
regeneration of myelin sheath, thus potentially providing an effective therapeutic
for MS patients around the world.
 |
Figure 1.
MS causes the immune system to destroy Myelin in the CNS. Specific aim one is
part of finding a component that may be vital to induce proper regrowth of
Myelin in patients with MS.
The
target MBP can be ordered at a reasonable price from United States Biological,
telephone number (800)-520-3011. Their website is http://www.usbio.net/. The
catalog number is M9758-10 and it cost $327.00 for 1 mg of MBP. If 400 pmol of MBP is
used per round of selection, the cost per round will be $2.42.
Boggs, J. M. (2006). Myelin basic protein: a multifunctional
protein. Cell. Mol. Life Sci., 63, 1945-1961.
Nastasijevic
B, Wright BR, Smestad J, Warrington AE, Rodriguez M, et al. (2012)
Remyelination Induced by a DNA Aptamer in a Mouse Model of MultipleSclerosis.
PLoS ONE 7(6): e39595. doi:10.1371/journal.pone.0039595
Smestad,
J., & Maher, J. L., III. (2013). Ion-dependent conformational switching by
a DNA aptamer that induces remyelination in a mouse model of multiple
sclerosis. Nucleic Acids Research, 41(2), 1329-1342.
http://dx.doi.org/10.1093/nar/gks1093
Here is a link to my progress report number 1: https://www.dropbox.com/s/yzecdo0awberv3e/Roberts%2C%20Evan%2C%20MBP_Progress_Report_1.pdf
Here is a link to my progress report number 2: https://www.dropbox.com/s/alddplzsckghtbd/Roberts%2C%20Evan%2C%20MBP%20Progress%20Report_2.pdf
Here is a link to my final report: https://www.dropbox.com/s/xrbxly8ojvn7gxw/Roberts%2C%20Evan%2C%20MBP%20Final%20Manuscript.pdf
Here is a link to my progress report number 1: https://www.dropbox.com/s/yzecdo0awberv3e/Roberts%2C%20Evan%2C%20MBP_Progress_Report_1.pdf
Here is a link to my progress report number 2: https://www.dropbox.com/s/alddplzsckghtbd/Roberts%2C%20Evan%2C%20MBP%20Progress%20Report_2.pdf
Here is a link to my final report: https://www.dropbox.com/s/xrbxly8ojvn7gxw/Roberts%2C%20Evan%2C%20MBP%20Final%20Manuscript.pdf
