The promise of minocycline in neurology

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

The promise of minocycline in neurology

Postby feesher » Mon Nov 29, 2004 8:55 am

In the latest Lancet Neuro:
<shortened url>

I actually bought the article out of curiosity, and I don't know if I should copy/paste the whole thing here. If it's kosher/legal, I will post it.

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Postby Arron » Mon Nov 29, 2004 11:29 am

If you paid for it, than you cannot post the entire article here... but you can post excerpts with a link to the source.

Thank you for asking AND offering!
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snips

Postby feesher » Mon Nov 29, 2004 11:45 am

Snips from the pub. that I think resonate with recent posts in various forums:

1) Inhibition of microglial activation - The expression of several molecules associated with microglial activation, including caspase 1 (interleukin-1 beta-converting enzyme) and inducible nitric oxide synthase, reduced expression after treatment with minocycline.

Whether minocycline has a direct or an indirect effect on microglial activation was investigated in tissue culture. Minocycline directly inhibited the proliferation and the activation state of cultured microglia. Microglial activation in tissue culture contributed to glutamate excitotoxicity, and microglial activation was reduced by minocycline with associated alleviation of excitotoxicity.

2) Suppression of free-radical production - The generation of free radicals, leading to lipid and protein peroxidation and damage to membranes is also a common mechanism across a spectrum of diseases. Minocycline depresses the release of oxygen radicals from various cell types, including leucocytes... the production of nitric oxide is decreased by minocycline through an effect on nitric oxide synthase.

3) Another mechanism for minocycline action that may account for its effect on various neurological diseases is its inhibition of MMPs. Various MMPs are upregulated in neurological disorders, in which they can contribute to demyelination, neurotoxicity, and neuroinflammation.

4) Other mechanisms may also contribute to the activity of minocycline. The drug is a Ca2+ chelator and may sequester excess Ca2+ released after injury. The decreasing of Ca2+ concentrations may prevent activation of calpains and preserve axonal integrity.
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Postby raven » Mon Nov 29, 2004 11:55 am

Good stuff Feesher...

Thanks.
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Postby OddDuck » Mon Nov 29, 2004 12:02 pm

Hi, feesher!

I echo the same. Nice explanation.

I also found some actions of minocycline (i.e. via caspase 3 inhibition) that was at the very least really interesting (and I'm sure fits in with what you have found).

Again, great post there!

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Postby Arron » Mon Nov 29, 2004 12:07 pm

Fantastic information. It would be wonderful for David Wheldon, Anecdote's husband, to take a good look at this article and see how it fits in with his research.
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I figured it was worth the $30 bucks

Postby feesher » Mon Nov 29, 2004 12:13 pm

:D
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Mincycline

Postby bromley » Tue Nov 30, 2004 1:41 am

Thanks for the post.

I have two observations:

(i) Why can't the article be posted (and the minocycline article in the Annals of Neurology of May 2004). The authors work for institutions which are funded by the taxpayer or charitable donations. The results of their work should be free - particularly to those suffering from this disease. I'd say post and be damned. Who can they sue? Would they want the publicity - 'ms researchers sue site used by ms sufferers'.

(ii) I haven't seen the results of the trial of ten MS sufferers who took minocycline, but the general sense I got was that the results had been good (not sure whether this meant reduction in exacerbations / number of lesions etc). What staggers me is that a larger trial is not being undertaken of treatment just with minocycline (there's a trial with Avonex). Surely a sensible Health Department could see the financial benefits if minocycline was shown to be as good as the expensive CRAB treatments. It must be worth investing a few million to potentially save hundreds of millions. Also, minocycline seems to be dealing with the heart of the problem - not just the immune response which many of us now believe kicks in afterwards. Not sure whether minocycline has any neuro-protective benefits - this is the area the researchers really need to get sorted. For too long the focus has been on reducing exacerbations but progress of the disease seems to continue. It might well be the case that if the immunce system could be totaly suppressed i.e. no exacerbations at all the disase would still progress - because as some of us have discussed on several occassions there's something else going on before the immune system gets inolved.

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Postby raven » Tue Nov 30, 2004 2:59 am

Hi Bromley

I can see your point regarding the posting of the full article, however the article is copyrighted and as such cannot be posted. We cannot decide for ourselves which laws we consider appropriate. In any case I believe that Feesher has posted the salient points, little would be gained by posting more.

Regarding the trials of Minocycline, they are happening albeit slowly. As has been stated before it is extremely expensive to run large scale clinical trials. Whilst such trials could potentially save millions they are a gamble. It takes the wealth of the pharma companies to conduct them properly. Even then the pharmas often have to share the costs, hence the tie-ups between Elan - Biogen, Biogen - Genentech etc.

The most promising news I have seen regarding Minocycline is Serono's statement that they are developing a non-antibiotic isomer. Hopefully, as an isomer of an already approved drug it will not have to go through the full FDA approval procedure and will become available much sooner because of this.

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Postby SarahLonglands » Tue Nov 30, 2004 5:50 am

Fantastic information. It would be wonderful for David Wheldon, Anecdote's husband, to take a good look at this article and see how it fits in with his research.


Arron, he might well when he has the time, but I thought I would just butt in here and probably in the process say just what he would think:

If minocycline or doxycycline are only useful for their neuroprotective qualities, then how is it that after six months of doxycycline I was switched, at Charles Stratton's recommendation to rifampicin, which is not neuroprotective at all and the improvements carried on. Now I have gone for two months without taking any antibiotics at all and the improvements are still slowly, bit by bit, carrying on. Basically, I have had no adverse event for 16 months now. Surely if the tetracyclines were only useful in MS for their neuroprotective qualities, after eight months without neuroprotection I would be feeling somewhat the worse for wear?

If you are taking any other drug, say betaferon or whatever, if you stop it any benefits you might have gained are lost, so I imagine it is the same for a tetracycline unless it is taken as an antibiotic to get rid of an infection.

Robin said:
The most promising news I have seen regarding Minocycline is Serono's statement that they are developing a non-antibiotic isomer. Hopefully, as an isomer of an already approved drug it will not have to go through the full FDA approval procedure and will become available much sooner because of this.


Surely this will mean that anyone taking one of the new non-antibiotic tetracyclines will have to take it continuously for full effect, not just be able to stop it, with the occassional booster dose for a couple of weeks every two or three months for a year or so?

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Postby raven » Tue Nov 30, 2004 6:32 am

Hi Sarah,
The above discussion does not counter the assertion that C. Pn. is responsible for a subset of MS cases. However the neuroprotective effect of Minocycline should be applicable to all cases.

It does mean that the drug will have to be taken for the rest of your life as it counters the effects of MS and not necessarily the cause.

Robin.
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Antibiotics in Treatment of MS

Postby coach » Tue Nov 30, 2004 9:13 am

Perhaps this has already been addressed, but was just wondering how the C. Pn. hypothesis of MS addresses the difference in the rate at which women as compared to men ( a 2 to 1 or 3 to 1 ratio) suffer from MS. I still am following the C. Pn. theory and antibiotic Rx on this website.
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Postby SarahLonglands » Tue Nov 30, 2004 9:54 am

Hello Coach,

This is just a shot in the dark, but do you think it might be because more men suffer from heart problems? More specifically, there is still a tendency for men to grin and bear things for longer than women, which is why they are often diagnosed later in life. C Pn is known to be associated with atherosclerosis and we were both discussing only last week the number of men who die from heart disease while only in their forties or fifties. It would seem to follow from this that maybe the proportions are slightly artificially skewed because many men die before diagnosis.

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Postby raven » Tue Nov 30, 2004 10:05 am

Again I am not going to dispute the C. Pn. theory. I myself am following the antibiotic regime. I must remember to update my regimens thread at some point :wink:

Susceptibility to MS involves a genetic component. Wesley (BioDocFL) has posted a very convincing argument as to why women should be more susceptible to MS than men. In his intial argument the antagonist was HSP-60 which is produced by C. Pn. but the antagonist could be LPS or even heavy metal toxicity.

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Postby Arron » Tue Nov 30, 2004 11:58 am

yes, raven and coach, updates are always very much appreciated. :)


I believe this is a good time to inject the Standard Legal Disclaimer on unapproved therapies:

Remember that antibiotic therapy is not formally approved for MS, and should be pursued only with the consent of your doctor. Any information you find on this site should not be considered medical advice - If you follow community member's opinions and/or advice, you do so at your own risk.

whew...
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