Much deeper understanding of MS and CCSVI at last!

[NZer1]

Hi everyone, I have tried to put this in simple words and also given two links to the details articles that give the required support!

MS is known to be linked to Immune system dysfunction and the process is beginning to be understood through extensive research of the function and pathways for Vit D to be effective. The findings that pathogens/infections are involved in the early stages of MS development, before symptoms commence and before technology can 'measure' the outcomes of the MS 'cascade', is helping to link all the dots.
The findings such as CCSVI and Vascular dysfunctions which create the breach of the blood brain barrier (BBB) and allow the blood to carry infections across into the central nervous system (Brain) where they are not meant to be and neither is the immune system from outside of the Central Nervous System (CNS). The CNS has it's own separate immune system within the Cerebo Spinal Fluid (CSF).
When the bodies immune system cells such as CD4 and T regs, enter the CNS through the BBB breaches, they are uncontrolled by the bodies immune system when inside the CNS and do damage to the Nervous System/Myelin because the bodies immune system cells are no longer directed by Vit D receptors as it would because the infection has caused problems with the conversion process of Vit D and/or has immobilised the Vit D receptors inside the CNS.

Re-setting the rogue bodies immune cells with calcitriol and Vit D treatments shows HUGE promise for PwMS and trials need to be established some how!!

Abstract
Multiple sclerosis (MS) is an incurable inflammatory demyelinating disease. We investigated one calcitriol dose plus vitamin D3 (calcitriol/+D) as a demyelinating disease treatment in experimental autoimmune encephalomyelitis (EAE). Evidence that calcitriol-vitamin D receptor pathway deficits may promote MS, and data showing calcitriol enhancement of autoimmune T cell apoptosis provided the rationale. Whereas vitamin D3 alone was ineffective, calcitriol/+D transiently increased central nervous system (CNS) Helios(+)FoxP3(+) T cells and sustainably decreased CNS T cells, pathology, and neurological deficits in mice with EAE. Calcitriol/+D, which was more effective than methylprednisolone, has potential for reversing inflammatory demyelinating disease safely and cost-effectively.
http://www.ncbi.nlm.nih.gov/pubmed/23968560
Full paper @;
http://fairyofdisenchantment.files.word ... _15_13.pdf

Regards,
Nigel

[1eye]

This looks like an outstanding result, even for EAE!

[PointsNorth]

Has their been any anecdotal reports of pwMS trying Calcitrol+vit.D? Who will wait for Phase III trial?

PN

[NZer1]

Hi PN, that's the point of me putting this out there.

The more PwMS who see this and then talk about it to many more people the quicker it will go from publication to trial and then the various Phases and acceptance.

Rather than wait 18 years for this to be accepted 'we' can move this to a time frame of 1-1.5 years to being mainstream!

1 Calcitriol pill plus Vit D top ups and a few blood tests to check the patients status over the year!

Imagine that, PwMS actually having an option that works and for $100-$150 PA ;)

Nigel

[NZer1]

Vitamin D3 Confers Protection from Autoimmune Encephalomyelitis Only in Female Mice1
Karen M. Spach* and Colleen E. Hayes2,†


*Department of Nutritional Sciences and
†Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, Madison, WI 53706


Abstract

The prevalence of multiple sclerosis (MS) increases significantly with decreasing UV B light exposure, possibly reflecting a protective effect of vitamin D3. Consistent with this theory, previous research has shown a strong protective effect 1,25-dihydroxyvitamin D3 in experimental autoimmune encephalomyelitis (EAE), an MS model. However, it is not known whether the hormone precursor, vitamin D3, has protective effects in EAE. To address this question, B10.PL mice were fed a diet with or without vitamin D3, immunized with myelin basic protein, and studied for signs of EAE and for metabolites and transcripts of the vitamin D3 endocrine system. The intact, vitamin D3-fed female mice had significantly less clinical, histopathological, and immunological signs of EAE than ovariectomized females or intact or castrated males. Correlating with reduced EAE, the intact, vitamin D3-fed female mice had significantly more 1,25-dihydroxyvitamin D3 and fewer CYP24A1 transcripts, encoding the 1,25-dihydroxyvitamin D3-inactivating enzyme, in the spinal cord than the other groups of mice. Thus, there was an unexpected synergy between vitamin D3 and ovarian tissue with regard to EAE inhibition. We hypothesize that an ovarian hormone inhibited CYP24A1 gene expression in the spinal cord, so the locally-produced 1,25-dihydroxyvitamin D3 accumulated and resolved the inflammation before severe EAE developed. If humans have a similar gender difference in vitamin D3 metabolism in the CNS, then sunlight deprivation would increase the MS risk more significantly in women than in men, which may contribute to the unexplained higher MS incidence in women than in men.
http://www.jimmunol.org/content/175/6/4119.full

[Rogan]

Nzer1. I for the life if me can't figure out how this paper further describes CCSVI.

As we know EAE is not MS. We've had 50 years to prove this.

Here is the latest explanation for CCSVI. Dr Hubbard.

Here he explains his theory for how hypoperfusion in the brain kills the oligdendroytes, which are cells that make the myelin which starts the whole cascade we call MS.



Here are some cool slides from the presentation:

Overview:

Auto immune theory Status
Oligodendrocyte apoptosis (death)
Hypoperfusion and CNS venous drainage
BBB permeability
fMRI BOLD venous undershoot Study
Perfusion Study
Venoplasty summarized
Clinical Outcomes of Venoplasty Study
Conclusions and Recommendations


Slides on the work of John Prineas and Michael Barnett who proved that

Oligodendrocytes die first, white cell enter later

His slides showing the prefusion Pre and Post Venoplasty

His conclusions

Auto-immune theory is unproven
Immunosuppressant drugs are marginally effective and incredibly expensive
Oligodendrocyte damage may be primary and may be related to poor venous flow and hypoperfusion
Preliminary evidence of efficacy for venoplasty

His Recommendations

Don't discontinue your DMD's
Double-blind studies are planned
But, study design is complex
MS-MRI plus MRV and MR perfusion (ask you docs for an MRV and MR perfusion report when your getting you MS check up)
If abnormal, consider venoplasty
Learn about what else you can do to be proactive, Google Scholar
Double-blind vs Double-Hope.

[NZer1]

Hi Rogan the bottom line in MS appears to be the breach of the BBB and the leak into the CNS of the bodies immune system is one of the issues that happen.

If those immune cells are not managed by the automatic apoptosis system of the bodies immune system then there are cells that cannot be shut off, CD4 T cells and they are the ones that are found around lesions.

The challenge is to find out if these cells 'start' the destruction of the myelin or whether they are the 'clean up team' that doesn't stop because they are no longer controlled by calcitriol and the bodies immune system processes because the immune system within the BBB/CNS is different to outside the BBB/body.

Not sure if I am making sense here but the main issue is leaking BBB and stopping that from occurring regularly is the point of MS research in CCSVI.

The use of EAE in Prof Hayes research is to create a breach in the BBB and she has used several different infectious agents to do her experiments to make sure it is not the infective agent/pathogen used that is causing the damage in the CNS.

So different agents/pathogens created the same problem with the bodies immune cells (CD4 T cells) damaging myelin and not the infective agents/pathogens themselves. So it doesn't matter what starts the BBB breach and immune response, it is shutting down the CD4 Tcell reaction that is the problem in MS in Prof Hayes studies.

[1eye]

I read one report of one person who died from "MS" because her heart stopped because the damage was to a nerve that controlled her heartbeat (this is just from memory) and the one thing they found in addition to that was that oligos were having programmed cell death. If that caused the immune system all of a sudden to attack myelin (because the debris would have included myelin the oligo was busy making) that might get the T-cells busy if they didn't know the oligos had snuffed it on purpose-like. They might make out myelin to be an antigen of interest. So the way things go down is suggested to be that the suicidal Ollies were signaled by the microglia. that were activated because of circulating fibrinogen being converted to fibrin by thrombin, which was happening because pressure above the stenosis had breached the BBB in the thin-walled veins. Or reflux, or both. Thrombin, when you bleed, starts clotting. Questions in my mind have to do with iron. Is iron perhaps from blood cells extravasated through the breach, and is iron the blood component that brings thrombin to the breach site?

I guess what I'm saying is, are these scleroses really scar tissue, a clot on the brain side of the BBB?

I keep forgetting that nothing works as it does because any of these cells are thinking anything out. They do things the way they do because of millions of years of more and more successful evolution, which doesn't work much past breeding age.