Single Calcitriol Dose Beats Back EAE in Mice

[Frank]

Looks interesting. Any thoughts on this?
http://www.msdiscovery.org/news/new_fin ... k-eae-mice

--Frank

[HarryZ]

Looks interesting. Any thoughts on this?
http://www.msdiscovery.org/news/new_fin ... k-eae-mice

--Frank

Over the years there have been many drugs that have shown a lot of promise when they have dramatic results when tested on the that poor MS mouse. My wife took part in a trial many years ago with a drug that stopped and reversed EAE in the mouse. After about a year into the trial, a patient died because of the damage the drug did to his heart and the trial was stopped. My wife was on the placebo.

To date, there hasn't been anything that has worked wonders on the mouse that has translated into success for human MS. Hopefully this discovery will work out differently but I wouldn't hold my breath.

Harry

[CureOrBust]

Due to steroid usage, I was found to have low bone density, and was prescribed calcitriol. I do not remember it having any effects on my ms at the time, which was pretty mild at that stage.

[Squeakycat]

Looks interesting. Any thoughts on this?

YES. We have been discussing this in the Vitamin D thread.

[euphoniaa]

Looks interesting. Any thoughts on this?

YES. We have been discussing this in the Vitamin D thread.

In the interest of clarity, I assume that Squeakycat is referring to the Vitamin D discussion in the CCSVI forum here and NOT the multi-thread, 63 page, convoluted conglomeration of conversations in the “Natural Approach” forum titled “all things vitamin D.”

Here’s a link to the Vit D thread in the CCSVI forum, titled: "Vit D3>125nmol/L min in blood. FIRST SMALL STEP for pwMS"

http://www.thisisms.com/forum/chronic-c ... 14805.html

P.S. I see that Squeakycat has now found, and posted on, the other Vitamin D thread also.

[PointsNorth]

Does anyone know of a human animal withMS that has tried a single dose of Calcitriol greater than say 10mcg? CureorBust?

PN

[centenarian100]

“There are more than 100 compounds of proven efficacy in EAE, and we believe that it is pointless to add anymore to this list” -Sriram & Steiner

Source: http://www.ncbi.nlm.nih.gov/pubmed/16315280

not to discount EAE, but no need to get too excited

[Squeakycat]

Does anyone know of a human animal with MS that has tried a single dose of Calcitriol greater than say 10mcg? CureorBust?

PN

As far as I know, the highest studied dose was 2.5 mcg/d in Wingerchuk and an Iranian study which I can't put my hands on at the moment. To minimize hypercalcemia, high doses of calcitriol are normally given as a weekly or twice-weekly pulse dose which would have been the equivalent of 17.5 mcg administered once a week.

There is testing in cancer patients of doses up to 168 mcg oral and 74 mcg IV.

A human trial of the Hayes finding is likely to start at the 2.5mcg - 5mcg level that is currently approved by the FDA for use in managing calcium in renal failure since that would be the normal conservative approach to testing this with escalation from there up to a point where positive effect is seen or hypercalcemia is induced.

[Squeakycat]

“There are more than 100 compounds of proven efficacy in EAE, and we believe that it is pointless to add anymore to this list” -Sriram & Steiner

Source: http://www.ncbi.nlm.nih.gov/pubmed/16315280

not to discount EAE, but no need to get too excited

EAE is not MS and mice are not humans. I haven't read the study you quote other than the abstract, but I think there is only one well known case where something that was as effective in EAE as calcitriol + D3 absolutely failed to have effect in MS and that was inoculation with myelin basic protein.

Hayes directly compares the effect of methylprednisolone with calcitriol + D3 in her mice and shows that the latter was vastly more effective. She also looked at the literature and compared the effects of calcitriol + D3 against shipping drugs such as Tysabri, interferon and Copaxone and shows that the former was far more effective and without unintended side effects.

Further the Hayes lab has been looking at this in EAE since the mid-1990's at the level of immune cells which are known to be parallel between MS and EAE so that there is a considerable body of knowledge built up around the lowest level mechanisms in EAE that have parallels in MS.

Without getting too emotionally invested in this, I nevertheless think there are some very good reasons to do some basic testings in pwMS to see if this has the same effect:

• ** It is an approach which supports, rather than suppresses the immune system.

• ** If it were to work, it is a solution that costs around $50 a year or less compared with the nose-bleeding price levels of other MS drugs.

• ** Calcitriol has been used in human medicine for over 20 years and adverse effects are well known and manageable.

• ** Since it is a based on a single, albeit high, dose of calcitriol, side effects should be minimal and transient and are far less than those associated with shipping MS DMDs.

• ** The control of the local, adaptive immune system by calcitriol is well known, studied and tested in humans.

• ** Hayes has identified a plausible mechanism to explain the immortality of certain pro-inflammatory immune cells in MS and directly measured the effect of a single, high dose of calcitriol on this problem in EAE.

I'm sure there are other things that could be added to this list, but not at the end of a long day. :>)

I can think of no reason why this shouldn't be tested to see if it works in pwMS and am happy to keep my emotions in check until the results of that testing are known.

[want2bike]

I think most accept that vitamin D is important in treating MS. Why not buy the vitamin D3 over the counter. Why do the mice get better but the people do not? All disease is about deficiency and toxicity. Vitamin D may not be the only thing we are deficient in. There are a number of vitamins and minerals we need for good health. With the toxicity issue I am sure the mice do not have a mouth full of mercury fillings. They probably did not get the flu shot. They do not brush their teeth with fluoride every day. They are not taking other drugs. When people start eating the nutrition the body needs and stop putting toxins in the body they get better. The body was design to heal itself. We just have to give it what it needs.

[Squeakycat]

I think most accept that vitamin D is important in treating MS. Why not buy the vitamin D3 over the counter. Why do the mice get better but the people do not?

This is the key finding in the Hayes study: Over the counter vitamin D3 has to be converted to the bio-active form, calcitriol. Something in MS or the immune response to the disease is blocking that conversion in the CNS.

The mice do not get better with vitamin D3. They only get better after taking the single dose of calcitriol, bypassing the problem of conversion of D3 to calcitriol.

That not only immediately sets of programmed cell death of pro-inflammatory immune cells and the proliferation of anti-inflammatory immune cells, it resets the system so that conversion of D3 to calcitriol then works.

At that point, the disease is kept in remission by over the counter D3.

This doesn't fix venous malformations or necessarily allow the immune system to deal with an existing viral or bacterial infection. Nor does it allow you to eat bad foods or not exercise. It simply puts the immune system back on track.

There may well be some people with deficiencies who will not be helped with this until those deficiencies are fixed.

[want2bike]

Vitamin D3 is cheap. Maybe the research are working on a form of vitamin D which they can sell us for a lot of money. They like to take things found in nature and get a patient on them. Best to have your vitamin D level checked to make sure you are not deficient. Problem with the study is people are looking for one thing to make them get better and it is not about any one thing. They will never come up with a quick fix because there isn't one. It is all about the total of everything we do to our bodies.

http://www.naturalnews.com/027345_Vitam ... e_sun.html

[Squeakycat]

Vitamin D3 is cheap. Maybe the research are working on a form of vitamin D which they can sell us for a lot of money.

Professor Hayes has been studying the link between Vitamin D and MS for over 30 years. Calcitriol is a prescription medicine, but the dose needed for humans based on her mouse study has a cost of $1.67 with a little extra for shipping and putting it into a capsule.

Calcitriol was discovered in the group she works with at the University of Washington ages ago and has been in use in human medicine for about 20 years.

She is 100% about finding a way to help people with MS, not developing an expensive, proprietary drug.

Her challenge was finding why, given all the genetic, environmental, clinical and other evidence of a link between vitamin D and MS, vitamin D3 alone provided so little benefit. The answer was that it was not being converted into the bio-active form, calcitriol, in the CNS of people with MS.

Calcitriol is not a proprietary drug. It is simply the bio-active form of vitamin D3 which is normally made in the kidneys and in every cell in the body.

[Kronk]

Vitamin D3 is cheap. Maybe the research are working on a form of vitamin D which they can sell us for a lot of money. They like to take things found in nature and get a patient on them.

I fear that Want2Bike is the same individual as Eat2BWell on the SwankMSDiet forum who is constantly posting ridiculous information such as government conspiracy over chemtrails, vaccine poising, mind control etc. She follows this up by blaming the onset of illness and insulting those of us with MS as she does not have the disease. I see she is better behaved here likely due to the work of site moderators which the Swank forum lacks…

In any case, this research is incredibly interesting. I believe that MS is likely many different diseases which present similar symptoms which could explain why some therapies such as LDN, DMDs, diet, CCVSI, chemo and so on work for many but not all. Would also indicate why scientists have not found the primary cause of illness, because there could be many. I personally try every therapy with some shred of evidence behind it in the hopes of finding a way to stabilize my particular form of MS.

[Squeakycat]

In any case, this research is incredibly interesting. I believe that MS is likely many different diseases which present similar symptoms which could explain why some therapies such as LDN, DMDs, diet, CCVSI, chemo and so on work for many but not all. Would also indicate why scientists have not found the primary cause of illness, because there could be many. I personally try every therapy with some shred of evidence behind it in the hopes of finding a way to stabilize my particular form of MS.

The research really does appear to be a major breakthrough and as such, worth testing in pwMS as soon as possible.

While there may well be many causes of MS such as CCSVI, EBV, a stealth bacterial infection, or even some combination of several of these, there are some things that remain constant. There is always a breakdown of the Blood Brain Barrier. There are always, immortal, active, pro-inflammatory immune cells. Genetic and environmental studies show a common link to vitamin D deficiency.

EAE mice are genetically very homogeneous compared with the genetic diversity of pwMS. The "cause" of EAE is different than all the various possible causes of MS.

Still, calcitriol controls the local, adaptive immune response so there are reasons for thinking that directly providing calcitriol rather than vitamin D3 will have effect regardless of the underlying causes of MS in each person.