This Is MS Multiple Sclerosis Community: Knowledge & Support

Also, when I first got sick and started doing a lot of research and read about the latitude gradient in MS and how it was suspected that this may be the result of sun exposure and vitamin D the first question I had to ask myself is why hasn't this been fully investigaged? This theory has been around for almost 30 years and not much has been done about it. I think the National MS Society has really lost sight of what they should be doing.

But here is an interesting video presentation regarding the initiation of clinical trials:

http://youtu.be/a8qh-wXN578

Hi CV,

Watched the vitamin D video. Very interesting. I am looking forward to a clinical trial, if/when it ever happens. (Of course the drug companies have no incentive to support such an endeavor).

Of all people, I thought you would like this paper (just in case you haven't seen this specific Mayo Clinic publication before) since it has info beyond just HSCT. . . . .

Immune Reconstitution After Autologous Hematopoietic Stem Cell Transplantation

http://download.journals.elsevierhealth ... 623884.pdf

- George

Hi George,

That is an interesting article in that it suggests that after HSCT the thymus is involute and the T cell reconstruction is due to memory cells that
are remnants after the HSCT treatment:



I think this article was written before the acceptance of the discovery of regulatory T cells. These cells act as moderators of the immune system and prevent autoimunity from occuring. Here is a pretty good paper that descibes these cells:

http://www.smccd.edu/accounts/digennaroc/biology430/Articles/Regulatory_T-cells.pdf

So, this peaked my interest to see what happens to regulatory T-cells (tregs) after HSCT. According to the paper below, the regulatory T-cell subpopulation quickly becomes normal within 9 months.

http://www.jci.org/articles/view/41072


Granted this is for allogenic HSCT, but it may be that the Treg/Teffector cell population increases after HSCT which would explain why the non-myeoblative procedure works also (note that Tregs are a type of CD4+ cell, but are usually a small proportion, about 5% if memory serves me correctly).

At any rate, it seems people with MS have defective regulatory T cells. http://www.ncbi.nlm.nih.gov/pubmed/17099776

So it could be that the cause of MS is not simply autoreactive T-cells but could be because the role of the regulatory T-cells are deficient in people with MS and allows autoimunity to happen.

Incidentally, to tie this all together, it appears the Vitamin D has the ability to enhance regulatory T-cell function:

http://www.plosone.org/article/info:doi/10.1371/journal.pone.0006635

All great points that make sense the way you describe them, CV. Also, for up to ten years post-HSCT the CD4+/CD8+ ratio remaining inverted (favoring CD8+ suppressor cells) may also play a factor since there may be a strong bias to supress self-intolerant CD4+ cells during this time.

Interesting that I just noticed that one of the authors of the paper I cited is Prof. Dreger. He was one of the clinical doctors on staff in Heidelberg that made daily rounds in the transplantation treatment ward to check on patients so I saw him nearly every day. A totally humorless guy (I never once saw him smile), but a smart doctor. I had a lot of great scientific discussions with him regarding HSCT for autoimmune diseases in general. He was very conversant on the topic.

Yeah most Gemans I have met dont have a sense of humor.

Here is a good video presentation regarding what is thought causes MS (Vitamin D & EBV as well as genes):

http://youtu.be/yAU3R8hq_2Q

Also, here is an excellent video presentation which talks about genetics, stems cells and why people with MS
have different levels of dissablities:

http://youtu.be/DZwWlDYMTio

Here is a good review article about the effect of Vitamin D on the adaptive immune system:

http://www.sciencedirect.com/science/article/pii/S1568997211001042

In regards to the theory that neurdegeneration is secondary to demylination of the axon, here is an interesting paper that
looks at a specific protein at the meylin-axon interface known as myelin-associated glycoprotein or MAG for short:

http://www.jneurosci.org/content/29/3/630.full.pdf

So, it is thought that the process of neurodegeneration begins when enough of the meylin sheath is destroyed and the MAG component is no longer present
to protect the axon.

In this study, they used mice that were breed withouth the MAG protein in their DNA. These are known as MAG knock-out mice. The result is that although there
appeared to be no problems with the meylin sheath, the axonal numbers were reduced by 28% in these mice over a 15 month period compared to healthy mice.

Here is a good article that describes the status of MS reseach including comments by the leading scientists:
http://www.dana.org/news/publications/detail.aspx?id=24568

Included in this group is a description of the work being done by Dr. Burt at Northwestern: