The promise of minocycline in neurology

A forum for the discussion of antibiotics as a potential therapy for MS

Postby raven » Tue Nov 30, 2004 12:09 pm

Arron, absolutely!

All medications that I take are done with the full knowledge and consent of my doctor. This site is fabulous for information but is no substitute for discussion with a qualified medical practitioner.

I have no more formal medical training than a goldfish! I would be horrified if I learned that anyone had done themselves harm through taking medication as a result of anything that I had posted

Robin
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Postby finn » Tue Nov 30, 2004 12:33 pm

Sorry, time to leave the board.

-finn
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Postby OddDuck » Tue Nov 30, 2004 12:43 pm

Hi, finn!!

Naw....don't remove your post! It's nice to see "agreement" and support of people on this Board, also. And YOU are always a welcome sight!

Deb
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Postby Arron » Tue Nov 30, 2004 1:30 pm

Finn, you know we love you and I'm very glad to see you dropping in!

I suppose this post should be removed too... but wait, I would have to remove it... hmmmm infinite loop.

;)

Ignore us. We're having a moment.
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Postby bromley » Tue Nov 30, 2004 2:42 pm

Raven,

Thanks for the response to my post. However, I'm not convinced that a trial of just minocycline should be so expensive. 50 ms sufferers give their time for free to be on the trial; minocycline is a cheap drug; MRI machines are (in the UK) owned by the Health Service / hopsitals; and neurologists are generally employed by the Health Service.

Whats irks me is that minocycline is being trialled with copaxone, and the effectiveness of the latter has been questioned. This looks like another attempt by the drugs companies to keep their expensive drugs on the market.

If minocycline is shown to be as effective or more effective than the current CRAB drugs this would send shockwaves around the drugs companies. Minocycline is cheap, safe, and in tablet form (no needles).

As a UK citizen, at my diagnosis I was told that as I had only experienced one attack I was not entitled to start treatment with any of the CRAB drugs - I was told that I should go away until a second attack. In these circumstances, I think a neurologist should (based on the Canadian trial results) prescribe minocycline. It can't do any harm, and may well reduce the risk of a second attack or protect the nerves.


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Postby raven » Tue Nov 30, 2004 3:12 pm

Actually Bromley antibiotics can do harm, like any other drugs they have allergic reactions and side effects. However as you are suggesting, under qualified medical supervision I do not see why they can't be prescribed.

But, without trial evidence the effectiveness is entirely unproven. Yes MRI scanners are owned by the NHS but they don't have the staff to run them. There is currently approx 1 year waiting list for an MRI. A proper medical trial would require thousands of scans and the qualified staff to interpret the results.

If minocycline is shown to be as effective or more effective than the current CRAB drugs this would send shockwaves around the drugs companies. Minocycline is cheap, safe, and in tablet form (no needles).


You said it....

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Postby Arron » Tue Nov 30, 2004 5:09 pm

We had this submitted to us by one of our members via the BrainTalk Board... thought the hypothesis might be relevant to this discussion.


Copyright © 2004 Elsevier Ltd All rights reserved.

Chronic Lyme borreliosis at the root of multiple sclerosis “is a cure with antibiotics attainable?"

Markus Fritzsche ,

Clinic for Internal and Geographical Medicine, Soodstrasse 13, 8134 Adliswil, Switzerland

Received 15 September 2004; accepted 17 September 2004. Available online 11 November 2004.

Summary

Apart from its devastating impact on individuals and their families, multiple sclerosis (MS) creates a huge economic burden for society by mainly afflicting young adults in their most productive years. Although effective strategies for symptom management and disease modifying therapies have evolved, there exists no curative treatment yet.

Worldwide, MS prevalence parallels the distribution of the Lyme disease pathogen Borrelia (B.) burgdorferi, and in America and Europe, the birth excesses of those individuals who later in life develop MS exactly mirror the seasonal distributions of Borrelia transmitting Ixodes ticks.

In addition to known acute infections, no other disease exhibits equally marked epidemiological clusters by season and locality, nurturing the hope that prevention might ultimately be attainable.

As minocycline, tinidazole and hydroxychloroquine are reportedly capable of destroying both the spirochaetal and cystic L-form of B. burgdorferi found in MS brains, there emerges also new hope for those already afflicted.

The immunomodulating anti-inflammatory potential of minocycline and hydroxychloroquine may furthermore reduce the Jarisch Herxheimer reaction triggered by decaying Borrelia at treatment initiation. Even in those cases unrelated to B. burgdorferi, minocycline is known for its beneficial effect on several factors considered to be detrimental in MS.

Patients receiving a combination of these pharmaceuticals are thus expected to be cured or to have a longer period of remission compared to untreated controls.

Although the goal of this rational, cost-effective and potentially curative treatment seems simple enough, the importance of a scientifically sound approach cannot be overemphasised. A randomised, prospective, double blinded trial is necessary in patients from B. burgdorferi endemic areas with established MS and/or Borrelia L-forms in their cerebrospinal fluid, and to yield reasonable significance within due time, the groups must be
large enough and preferably taken together in a multi-centre study.

Tel.: +41 1 710 93 43; fax: +41 1 710 93 44

Note to users: The section "Articles in Press" contains peer reviewed and accepted articles to be published in this journal. When the final article is assigned to an issue of the journal, the "Article in Press" version will be removed from this section and will appear in the associated journal issue. Please be aware that "Articles in Press" do not have all bibliographic details available yet.

http://www.sciencedirect.com/science?_o ... L&_aset=B-
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minocycline, CPn, etc.

Postby Daunted » Tue Nov 30, 2004 7:52 pm

First of all as far as the article being copyrighted, that's a complex issue but you will see more and more free articles online ala the British Medical Journal. That's the trend.

The minocycline stuff is difficult to sort out...but I believe Anecdote is correct that there is substantial evidence in favor of antibiotics treating an underlying CPn infection, rather than simply being neuroprotective...the huge problem from a scientific standpoint, of course, being that many people using antibiotics haven't had their CSF tested for CPn and those that truly do not have CPn infections may improve anyway!

The Siriam, Song, Moses, Stratton & Wolinsky presentation at the American Academy of Neurology clearly showed that antibiotics other than minocycline can be clearly efficacious when there is verified CPn infection- again, it'd be nice if I, for instance, would have been tested for CPn when I had my spinal tap.

As far as gender differences in MS and how that can be possible if a common pathogen is responsible, that is interesting. This is confounded by the likelihood that MS is hetergeneous so perhaps CPn is distributed somewhat uniformly but there are other causes of chronic demyelination that are biased towards females. Also, a gender gap seems plausible due to factors like smoking, for instance, and there appear to be some literature on this topic, like this article (http://iai.asm.org/cgi/content/full/69/5/2865) which finds that male rats get hit much harder by M. pulmonis respiratory disease, so perhaps there are genetic explanations or other plausible reasons for the gender distribution in MS that are not incompatible with CPn infection as a cause, in some cases at least.

I have a question, though: Assuming antibiotics and Aimsopro are theoretically both effective in the same MS patients, how would THAT be explained? I would love to hear the answer to that...
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Postby SarahLonglands » Wed Dec 01, 2004 1:07 pm

Interesting piece about borrelia, Arron. I will quote a piece from David's web pages because he has always maintained that MS might well be polymicrobial. Hence his choice of antibiotics.

In treating the disease, it makes sense to use agents which are effective against other potential pathogens of the CNS including Borrelia garinii and B burgdorferi. These have been known to cause a serologically negative MS-like illness. It would also make sense to cover for Rickettsiae and Mycoplasma sp.and cell-wall deficient forms. MS and other chronic relapsing-remitting but ultimately progressive diseases may have a polymicrobial phase: the punctured vasculitis caused by Chl pneumoniae would provide an easy portal of tissue-entry for blood-borne organisms.In treating the disease, it makes sense to use agents which are effective against other potential pathogens of the CNS including Borrelia garinii and B burgdorferi. These have been known to cause a serologically negative MS-like illness. It would also make sense to cover for Rickettsiae and Mycoplasma sp.and cell-wall deficient forms. MS and other chronic relapsing-remitting but ultimately progressive diseases may have a polymicrobial phase: the punctured vasculitis caused by Chl pneumoniae would provide an easy portal of tissue-entry for blood-borne organisms.


I was tested by an Enzyme-linked Immunosorbent assay for Lyme Disease at Southampton, the national centre for detection of such infections. My serology was negative, but then it can be negative in neuroborreliosis. I don't ever remember being afflicted by tick bites, though, just mosquitoes, to which I am was until recently very allergic. I was also only marginally positive for C Pn. If I had had a lumbar puncture there is no certainty that anything would have been found, so where would I be now?

You don't need to have ever lived in an borrelia endemic place to get MS, though; which is surely a blow to a Borrelia alone thesis. However, in a way this doesn't really matter because the antibiotics proposed both by David and by Marcus Fritzsche are effective for Lyme, C Pn infection and numerous other things.

As for your question, Daunted, about Aimspro.......

I have a question, though: Assuming antibiotics and Aimsopro are theoretically both effective in the same MS patients, how would THAT be explained? I would love to hear the answer to that...


........until we know that big trade secret, what all the antibodies used are, we can only guess!

Sarah
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Postby Daunted » Wed Dec 01, 2004 4:07 pm

Yes, but are monoclonal antibodies EVER known to be effective in treating bacterial infections? I'm not a biologist but that seems odd to me.
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Postby SarahLonglands » Wed Dec 01, 2004 4:20 pm

Ditto :?
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hmm

Postby Daunted » Wed Dec 01, 2004 5:51 pm

I did a quick lit search and there are many articles out there that state that monoclonal antibodies INCREASE the bodies vulnerability to infection....if you, Dr. Wheldon, or anyone else would care to guess how these two ideas are compatible, I would love to hear it.

If the hype about Aimspro is true, they are experiencing a very high rate of efficacy, so I assume it can't be the result of two different populations (one infectious, one auto-immune, for instance).

I also wonder why statins would treat an infection.

I'll be going on Dr. Wheldon's suggested regimen in less than a month, so 'I want to believe', as they say, but it will be helpful when some of these (highly theoretical) questions start to get worked out.

(I'm always the skeptic).
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Postby raven » Thu Dec 02, 2004 3:28 am

Hi Daunted,
The infectious cause and autoimmune reaction are not mutually exclusive. If you follow the 'grey matter' thread I and others attempt to postulate what might be happening. I would reiterate that it is all speculation though.

For a very simple analogy try and think of a row of standing dominoes. The first domino being infection, the last being neuron death and demyelinisation. In between there are several dominoes which represent microglial activation and MMP over-expression. In untreated MS knocking over the infection domino will cause all the others to fall in succession. If we can remove any one of them then the final domino, axon death and demyelinisation will not fall. Statins, minocycline etc. appear to remove the MMP domino. We don't really know how aimspro works so I can't comment on that. Of course treating the infection and stopping the first domino from falling is the ideal course of action, but it isn't proven that infection is the cause in all cases.

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combo?

Postby feesher » Thu Dec 02, 2004 8:42 am

Then I wonder... to cover one's bases...

What would a combo of antegren (just can't get myself to sue the new
name) and an abx (say, minocycline for infection and/or MMP9 downregulation and/or microglial deactivation). Take out 2 (potential) dominoes.

Who knows?

But let's say one had an infectious cause and took an abx, one would expect herx and/or relatively quick response, no? Would this differ if antegren is in the system? Would a bacterio-static abx like minocycline be effective if there are no leukocytes allowed in due to antegren.

And this is where I get over my head. I just can't connect that many dots.
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Postby raven » Thu Dec 02, 2004 9:37 am

Minocycline and avonex is actually being trialled. Minocycline will penetrate the BBB regardless of leukocyte inhibition so there should be a synergy between antegren and minocycline as well.

The above does not assume an infectious cause.

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