Thanks for the kind words!!
Yea, I think Robin and I realize we were getting a little "off" with our discussion.
Oh, yes, we knew it couldn't go too far. We WOULD be here "forever" on that debate! Apologies there.
Not to speak for Wesley, of course, or anything, but a lot of his theory was posted under the thread called polyamines. I think right now, he is fine-tuning his thoughts. That's an excellent question, by the way! I believe I even initially threw out a very similar question. Also, though, you probably might need to remember "replication" when speaking about mutation.
As far as therapy goes, gene therapy isn't as far off as you might believe (desipramine helps prevent DNA fragmentation, and TZD is also a type of gene therapy - that interestingly enough, they are testing right now for progressive MS and are having some success). Not to mention stem cell research. But having said that, you have a very valid concern.
Here are my thoughts:
MS is a combination of DNA, and other combinations of "triggers" such as Wesley has mentioned, there still remains a full "cascade" of myriad dysfunctional events that are produced once MS has been "triggered". I prefer to refer to it as the timing of the body is all off. There are/can be several points along and/or during this cascade of events where treatment and/or therapy can be focused (at the very least). As far as a "cure", IF any of us are anywhere NEAR to being correct in some of our assumptions (which call this ego, but I think we're just as close as anybody else....
), it MAY be quite a while yet before MS can be considered completely
preventable (either by vaccine or other methods of prevention). Not to sound negative, at all........but that is probably a realistic view of where our medical knowledge currently stands today. (Although, enormous strides are accomplished every day.)
But...........if we know what is triggering even SOME of the cascade events in MS (even if it is sort of like the chicken and egg teaser), then treatment should be able to be "taylored" to fit each individual to keep MS from exhibiting its presence fully. Right now, any therapies we have for MS just is not taylored specifically enough for MS. Not really. In MY opinion, so far, it has mainly been "let's throw THIS at it and see if it works". Maybe I'm a little wrong about that, but I'm an extremely detailed person, too, so it probably just appears that way from my perspective. Still, MS research has recently been finding ways to selectively target certain dysfunctions in MS, which is always exciting to me.
You know what is so coincidental? In touching upon MRI and quantum physics (maybe our conversation wasn't so useless after all......hehehe), the same type of pondering occurred to me. Knowing a little bit about how the MRI works, why isn't the MRI itself skewing or affecting DNA?
We all know what radiation does. I realize that the strength of MRI isn't that high, and all in all it is still a bit "crude", but you would think that MRI itself could be some form of treatment for SOMETHING. I might have to go look that one up. Of course, though, that truly gets us back into quantum. Phew!
I still believe the one thing the three of us still haven't factored back into our discussions is MHC. That's a biggie. There is enough research already that provides us with quite a bit of solid evidence for the huge role and involvement of MHC in MS. MHC traces right back to one or two specific chromosomes. Wesley is the expert at the front-end, though.
Here's an abstract that may help illustrate what I am referring to (remember, Wesley is involved in cancer research.)
Science. 1988 Oct 7;242(4875):69-71. Related Articles, Links
Distinct cloned class II MHC DNA binding proteins recognize the X box transcription element.
Liou HC, Boothby MR, Glimcher LH.
Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115.
The class II (Ia) major histocompatibility complex (MHC) antigens are a family of integral membrane proteins whose expression is limited to certain cell types. A pair of consensus sequences, X and Y, is found upstream of all class II genes, and deletion of each of these sequences eliminates expression of transfected genes. Furthermore, the absence of a specific X box binding protein in patients with severe combined immunodeficiency disease whose cells lack class II suggests an important role for these proteins in class II regulation. Here, the cloning of two lambda gt11 complementary DNAs encoding DNA binding proteins (murine X box binding proteins lambda mXBP and lambda mXBP-2) is reported. Both phage-encoded fusion proteins bind specifically to the X box of the A alpha, but not to E alpha or E beta class II genes. These two independent isolates do not cross-hybridize. The lambda mXBP complementary DNA hybridizes to two RNA species, 6.2 and 3.0 kilobases in mouse, that are expressed in both Ia positive and Ia negative cells. By means of DNA blot analysis with the lambda mXBP complementary DNA insert and probes generated from each end of this complementary DNA insert, lambda mXBP was found to arise from a multigene family. These data illustrate the high degree of complexity in the transcriptional control of this coordinately regulated gene family.
PMID: 3140376 [PubMed - indexed for MEDLINE]
If Wesley is on to something (which I believe Robin and I both have an inkling that he is), then epigenetics indeed plays a huge role in MS. The more I allow my mind to ponder on his information, the more it comes to me. Proteins and transcriptions are highly complex. But, if you will notice from the above information, the connection is there. We just have to fit all our musings into one.
And notice the point that Wesley expressed in his earlier post. To our minds, I believe, we can safely say that we have successfully broken through the dogma of MS being an "autoimmune" disease. We'll admit the autoimmune functions are definitely involved, but does MS originate
there? I'd say no.
EDIT: Oh, yea.....and where does norepinephrine factor into this? (Probably pretty early on in the cascade.) Easy..........as an example.........it fits right here:
J Neuroimmunol. 1988 Jan;17(2):89-101. Related Articles, Links
Norepinephrine inhibits gamma-interferon-induced MHC class II (Ia) antigen expression on cultured brain astrocytes.
Frohman EM, Vayuvegula B, van den Noort S, Gupta S.
Department of Anatomy and Neurobiology, California College of Medicine, University of California, Irvine 92717.
Recent evidence that astrocytes can be induced to express the class II major histocompatability (MHC) antigens suggests that these cells may be involved in the development of intracerebral immune responses. The principal inducer of MHC class II antigen (Ia) expression is a soluble lymphokine, gamma-interferon (gamma-IFN). Normally astrocytes do not express significant levels of Ia antigens despite the fact that agents such as gamma-IFN may be present in the central nervous system (CNS). Here we report that a major neurotransmitter, norepinephrine (NE), inhibits, in a dose-response fashion, the ability of gamma-IFN to induce Ia antigen expression on cultured astrocytes derived from newborn BALB/c mice. This finding may indicate that the brain contains inhibitory modulators that serve to prevent the up-regulation of intracerebral immune responsiveness.
PMID: 2826540 [PubMed - indexed for MEDLINE]