Does anyone use Clofazimine for AP?

[Serenity]

Hi all –

I just saw an article that says clofazimine is being tested for auto-immune diseases (it specifically mentions MS and Psoriasis). 

http://www.sciencedaily.com/releases/2009/01/090130182928.htm

I then looked up clofazimine and many articles say that due to its immunosuppresive properties it may be a good medicine for RA and other AI diseases.

Just wondering if anyone has any insights they can share about this drug versus minocycline.

Thanks!!

[Maz]

Hi Serenity,

Thanks for posting this link! 😀 It's a very exciting article in many ways. While I can't comment on how efficacious this antibiotic might be in RA or any other rheumatic disease, as it's new to me, too, what I found interesting was this bit in the article:

“One of the key steps involved in turning on the immune response is the prolonged accumulation of calcium inside of immune cells, Liu explains. When the researchers stimulated an immune cell, setting the signaling event in motion, they noticed that lots of calcium flushed into the cell and lingered there. However, when they pretreated the immune cells with clofazimine, the calcium rush was much less and it didn't hang around as long.”

What is so fascinating about this is that a similar, but slightly different action regarding T-cells and calcium are described in the New Arthritis Breakthrough. Here is a snippet from a post I made a while back:

…in The New Arthritis Breakthrough, by Henry Scammell. If you have the book, check out pg 280 in the section entitled: “Minocycline and the NIH Clinical Trials.” It is a brief overview on what provided the rationale for the further study of minocycline in the MIRA Trials…I would think the study is mentioned in the appendix, if you have a copy of the book to hand:

“Minocycline may help patients with rheumatoid arthritis because it eliminates an infectious agent. Alternatively, arthritis research in animal systems has shown the minocycline affects calcium metabolism or pathways in T Cells; and calcium pathways are a critical component of the ways in which T Cells activate themselves or function. T Cells exposed to minocycline take up too much calcium internally, and then become sick or malfunctional. They seem to quiet down, and the animals go into complete remission or are at least visibly improved by the therapy. This new information favors the possibility that some antibiotic drugs may be beneficial in rheumatoid arthritis because they eliminate these T Cell autoimmune responses, and not just because they home in on an infectious agent.”

So, according to these animal studies that were part of the fuel behind the MIRA studies, in addition to being used in the war waged against mycoplasma and other pathogens sensitive to it (like Lyme, for instance), apparently minocycline appears to have some effect as an immune modulator, which in turn has the effect of tuning down inflammation. This, bearing in mind that the above was based on animal studies. 😉

 

Clearly, both minocycline and clofazimine both have immune-modulating properties by altering how calcium is being used by T-cells…they're just doing it in different ways.

Minocycline has a number of different properties, including anti-bacterial, anti-collagenase, chelating effects and immune-modulating effects. What I'm inquisitive about is where clofazamine only works as an anti-baterial and immune modulator or whether it would also have anti-collagenase and chelating effects. If it doesn't, it may not work as well as minocycline for someone with a collagen-vascular disease. Hopefully more research will clarify these issues and it might hold potential as a nice alternative for people who can't tolerate the tetracyclines.

I wouldn't be at all surprised if at some point the parathyroid gland is found to play a much larger role in rheumatic/immune diseases than has ever been suspected.

Nice find and thanks again for sharing!

Peace, Maz

 

[kat]

Very very interesting, thanks for posting this!

I also found this very refreshing and encouraging:

“who uncovered the drug's latest potential during an ongoing and exhaustive screening of FDA-approved drugs designed to identify new uses for them. “

That's wonderful that they are looking at old drugs instead of just trying to develop new ones!

[Tiff]

Maz wrote:

I wouldn't be at all surprised if at some point the parathyroid gland is found to play a much larger role in rheumatic/immune diseases than has ever been suspected.

Can you elaborate on this, Maz?  My RA developed after my thyroid was removed.  Naturally, in that process, my parathyroids were shaken a bit – you have to remain in the hospital until your calcium levels stabilize after the surgery.  I believe I had one gland placed in the muscle as it did not “relocate” well.  That is not unusual with this surgery.  It was all very scary at the time. 

What might we look for with regard to the parathyroid and its role in maintaining calcium levels that influences AI diseases?  After the hospital testing, I don't recall them ever testing calcium levels again, not even in all the blood tests I had done for my RA.  If they did do them, they must have been normal.

Anyway, interested in your thoughts on this.

[Maz]

[user=45]Tiff[/user] wrote:

Can you elaborate on this, Maz? 

What might we look for with regard to the parathyroid and its role in maintaining calcium levels that influences AI diseases?  After the hospital testing, I don't recall them ever testing calcium levels again, not even in all the blood tests I had done for my RA.  If they did do them, they must have been normal.

 

Tiff, here is a good “layman's” outline of what the parathyroid glands do, including the actions of parathyroid hormone which controls the release and distribution of calcium throughout the body.

http://www.parathyroid.com/parathyroid-function.htm

Interesting to note that depression, fatigue and brain fog/memory issues are related to a malfunction of these glands, which is also very common in rheumatic disease. Not to mention that hyperparathyroidism has been implicated in certain cancers and heart disease, also something to which rheumatic patients are more predisposed.

The infection yersinia enterocolita (sp?) has been linked to thyroid disease and the parathyroid glands sit next to or sometimes in thyroid tissue. If a triggering infection sets off an “autoimmune” attack on the thyroid, it wouldn't be out of the realms of possibility that the same infection has some effect on parathyroid function…but this is just speculation on my part. 😉    

The other question arises, what is normal for one individual with parathyroid hormone and lab markers for calcium reference ranges may not be for another…this is certainly true for thyroid disease and TSH. It also seems that calcium fluctuations can occur and one lab test may not give the full picture in a long range situation. I just don't know, Tiff…I don't know enough about the parathyroid gland to formulate an informed opinion.

It just makes some sense to assume that if this gland is involved in calcium distribution and uptake within the body, there may be some triggering element that upsets this balance. Sorry I can't be more specific.

Peace, Maz      

[Tiff]

Thanks, Maz.  I just find it interesting that these paths keep crossing, yet my doctors never seem to notice.  They just tell me it is all random that I have had this array of problems.  It also interests me that they never take your parathyroid or calcium levels again once you leave the hospital after a thyroidectomy.  I guess I also wonder about it because I have lots of RA pain in and around my neck – often it feels like it is my tonsils, then deeper, causing pain when I swallow.  Very disconcerting pain for someone with a history of thyroid cancer.  I also have pain in my jaw and occasionally my actual neck or maybe the connecting joints of my shoulder to my neck, but what really puzzles me is the gland-like pains.  I still feel this area is where my infection got hold.  Weird, like all of this!

[Maz]

Hi Tiff,

I agree with you – very strange that these paths keep crossing. I'm just a layman patient, but I have no doubt that these organisms do a number on the endocrines, steal sterols from the body and upset all kinds of hormonal cascades as a result.

Check out this new article that has just linked Vit D and its lack thereof to the development of MS:

http://www.cbc.ca/health/story/2009/02/05/ms-vitamin-d.html#socialcomments

What irks me about this is that it makes it sound all so simple…a lack of Vit D in pregnancy or childhood triggers a gene that some people carry to cause MS. What it fails to comment on is why there are still some people in the northern hemispere who carry the MS gene variant,  DRB1*1501, but never develop MS.

Cell wall deficient, intracellular organisms are voracious consumers of sterols, needed to maintain their outer lipid layers. They'll steal it from the host wherever they can find it in good quantity, even if it means lining arterial walls to create a bit of inflammation in order to attract a cholesterol bandage (a plaque). Isn't it interesting that similar plaques are found on the myelin sheaths of those with MS?

What the above article is saying is that people with this MS need to supplement with Vit D as early as possible to avoid MS. How do they know this for certain unless they have studied people carrying this gene and supplementing with Vit D for their whole lifetimes?  My guess is that thes researches have made a simple assumption about causal relationship without questioning why some people with this gene variant and low Vit never develop MS.

There is no doubt that people with rheumatic diseases generally have low levels of Vit D….but why? It's not because they're not absorbing it correctly, because supplementation brings those levels back up. “Something” is sequestering Vit D and waylaying it, because the western diet is full of Vit D now and there is no reason for anyone to suffer from a deficiency.

I've decided to come back in my next life and get to the bottom of this! Like you, I seem to only get so far and go round and round in circles, looking carefully at one side of the argument and the other, but always finding missing pieces I can't quite find an answer for and throwing in the towel. It makes no sense that as a patient with RA the sun makes me feel wonderful within about 20 mins – better than taking Advil – but that for my brother with MS, he flares and can't sit in or tolerate the sun, at all. The only way I can rationalise this is that neuro-inflammatory diseases are just reactive to immune suppression a different way. Whereas people with RA flare in fall (after enjoying the summer sun and the increase in Vit D levels that brings), people with MS must be instantly reactive because of nerve involvement.

Tiff, I'm so sorry you have these concerns over the neck pains. I know you get checked and scanned regularly, so this should alleviate some of your fears…not all, I know, but if your parathyroid glands are also concerning you, maybe you could find a good doc who will do all the necessary labs and tests to check on this gland's function. Being so close to the thyroid gland and cancer having some ties to calcium balance in the body, I can see why you are questioning this. I am, too, and it sure would be nice to have some answers.

Hope you don't mind me sharing the MS stuff above, but I think you once mentioned you had a cousin with MS and thought you might find it interesting. 😉

Peace, Maz

[Tiff]

This is fascinating.  Thanks for the article.  At least the researchers are looking at more than just simple correlations, although the idea that those genes do only one thing and this is how it works is too simplistic.  They know that, but they can't help themselves, I think.

Wouldn't it be so nice if we could just take massive doses of vitamin D and get well?  I wish!  It alarms me that they tend to imply that, or that if you take massive doses you won't get sick.  It is not the first time they have made such suggestions for vitamin use, but with D I think it is even scarier because its role in the body is so poorly understood.  Heck, I guess that is true of vitamin C and E, also, but somehow it seems those “wonder vitamins” have been relagated to something more modest now days.

On another twist, I'd have to hunt for it, but I found an interesting article discussing the process of evolution.  It was saying that scientists are hitting a dead end with the concept of evolutiontion as a tree.  Typically it is thought that genes and traits are passed along in a linear fashion from parents to offspring, but the patterns they are finding in micro world are not bearing that out.  It appears that changes occur across the “tree” in a horizontal manner.  What I take this to mean is that the microscopic world (bacteria, fungus, viruses, etc.) can hybridize or pass genetic material across species creating a vast web of possible changes that render the concept of genetics even more complex.  And this can and does apply to multi-cellular organisms!  This ties into the idea of these pathogens actually messing with our genetics.  What if the genes they are finding in people with MS have already been altered by disease?  Apparently we are not pure genetic blueprints coming to fruition over the course of our lives, but rather “works in progress.”  At times it seems the farther we get, the more obvious that the complexity is more vast than we had thought.

Your right about how it starts to seem we aren't getting anywhere.  I think I'll pass on coming back to find out the answers.  Where I plan to go, the problems will have already been solved.  I'll enjoy finding out the “rest of the story” though!

My half-sister has MS.  She lives in Arizona and has enjoyed a lifetime of sunshine in addition to her D filled diet.  I spent my childhood in Colorado… long winters but lots of sunshine.  What about your brother?  Cold climate person?  And you?  One thing that she and I have in common though is that we both had very stressful childhoods with parents that were less than attentive to our needs.  This despite the fact that we grew up totally apart.  I suspect that long term, chronic stress on developing bodies isn't helpful to the immune system either, but there doesn't seem to be a lot of research in that direction either.

Honestly I don't fret over the thyroid cancer too much.  Apparently RA has such a multitude of manifestations that strange pains are pretty typical for it.  Thyroid cancer I would probably not feel until it was very advanced, and I'm getting tests run yearly that would most likely detect it way before that.  I do find it interesting how much RA symptoms vary!  Lots of people mention rib pain, which I think I may have had one time, but not very badly.  Other people it seems to focus in other places.  That is another interesting thing about it.  Why does it vary so much from one person to another?  For me it makes it hard to gauge my own progress.

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