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Medical News Today
Trial Shows Minocycline Has A Harmful Effect On Patients With Motor Neuron Disease
01 Nov 2007

Minocycline has a harmful effect on patients with amyotrophic lateral sclerosis (ALS)-commonly known as motor neuron disease or Lou Gehrig's disease-according to one of the first randomised trials of the drug in patients with a neurological disorder. This has implications for several trials that are planned or in progress for minocycline in patients with Huntington's disease, stroke, dementia, and multiple sclerosis, according to an Article in The Lancet Neurology to be published Online, Thursday, November 1, 2007.

Minocycline is an off-the shelf anti-inflammatory and anti-apoptotic drug that is neuroprotective in animal models of stroke, trauma, and neurodegenerative disorders, and also prolongs survival and reduces motor neuron loss in transgenic mouse models of ALS. Phase II trials suggested that minocycline could be taken safely by patients with ALS. On the basis of these positive results plans were made for many trials of minocycline in neurodegenerative conditions.

Dr Paul H Gordon (Columbia University, New York, USA) and colleagues in the United States Western ALS Study Group did a randomised phase III trial to test the efficacy of minocycline as a treatment for ALS in 412 patients. Compared with patients who took placebo, minocycline-treated patients deteriorated at a 25% faster rate according to the ALS functional rating scale (ALSFRS-R), and showed non-significant tendencies towards faster decline of forced vital capacity (FVC) and muscle strength.

In light of these findings, the authors suggest that trials of minocycline in other neurological diseases should be reassessed, as minocycline might be detrimental in patients with neurological diseases other than ALS. They conclude: "Our results are contrary to many published reports from laboratories, and thus have implications for trials of minocycline in patients with other neurological conditions, for the preclinical evaluation of potential neuroprotective therapies, and for the design of future clinical trials in ALS".

In an accompanying Comment Dr Michael Swash highlights the need for early diagnosis in ALS: "Clinicians and patients alike would prefer ALS therapy to be tested as early as possible, but there are unresolved difficulties with accurate early diagnosis, particularly the absence of a specific diagnostic test. Might some of the compounds that have failed in clinical trials show benefit if tested at disease onset in human beings?" He concludes that the time has come for new approaches to trial design: "The aim must be to design informative, short, inexpensive, and sensitive phase I/II studies before large phase III studies are attempted".

http://www.lancet.com

Article URL: http://www.medicalnewstoday.com/articles/87261.php

While my initial reflex is to become alarmed by this... I really don't think they can apply this to MS. If this where the case then Dr. Metz and Dr. Yong wouldn't proceed with more research on this for MS. I myself haven't had any problems since I've been on Minocycline, and while that could be a natural remission, it certainly hasn't invoked a relapse. I am not sure how I feel about this article though. Thanks for the post.

Brock

I am concerned both because I worry about creating more harm to myself and because I worry that my doctor will stop renewing my minocycline prescription.

The results from the new, larger, Calgary study probably won't be available until June 2010. Although given this latest research and warning regarding ALS, hopefully the Calgary doctors will publish interim information -- especially if they see a bad trend.

Hopefully I am not too biased by what I want to see, but the Calgary/minocycline journal articles seem more competent than the recent ALS/minocycline journal article. For example, the ALS article briefly discusses the dosage difference (200 m.g. b.i.d. in the ALS study compared to 100 m.g. b.i.d. in the small Calgary study) and concludes that the dosage didn't make a differnce, but doesn't seem to give any real statistics to show how they arrive at their conclusion. Likewise, the ALS article mentions that 2/3 of the patients were also on a standard ALS drug, but then seems to casually conclude that the results were consistent between the 1/2 of 1/3 of the group not on the standard drug but getting minocycline compared to the 1/2 of 1/3 of the group not on the standard drug but getting placebo. However, I didn't see any statistics to substantiate this conclusion either. Those kinds of details are more fully discussed in the Calgary journal articles, and I don't recall seeing conclusions without statistics in the Calgary articles. (Although, since I am new to reading these journal articles, I don't know if the Calgary people-study is more detailed because it involved fewer patients.) The ALS article also mentions that in their mouse studies, the mice were innoculated with the Minocycline before the disease -- which is not how things could work with people. However, in the Calgary study, the mice were innoculated with the disease and showed symptoms before receiving Minocycline -- which was then effective. Who knows if these things make a difference, but they make me a bit less confident in the ALS study.

I didn't see the phase 1-2 ALS study results, but at this point I am comforted by the early phase Calgary study results. It's only 8 or 9 people on the Minocycline, with no control goup, but they have been on it for 3 years. As a group they had very active disease before treatment, and very little disease for the three years following. I am also comorted by the anectdotal information I am getting on this forum and others. I have read at least one comment from someone who seemed to get worse, but most comments have been positive

I am definately worried about the results from the ALS study, but at this point I still want to continue the Minocycline and hope the Calgary doctors get out some interim results ASAP.

I also thank God I don't have ALS.

I don’t know if this has already been posted, but a presentation on the minocycline research in Canada was given at ACTRIMS 2007. In addition to the other trial outcomes that have already been reported (significant decrease in relapses and lesions), they also reported a decline in atrophy.
Long-term outcome of minocycline in relapsing-remitting multiple sclerosis (P10, page 24 of the pdf)

The other new info I noted when I read the abstract was that they used a 3T MRI.

So, while the news about the ALS trial is disconcerting, I’m still optimistic about the potential of minocycline.

Sharon

Furthermore the findings that tetracyclines have a poor effect in ALS is old hat as per this Lyme disease link where they found using a stronger metronidazole more effective. http://www.lymenet.de/indexordner/ials.htm

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3 years antibiotics, 06/09 bilateral jug stents at C1, 05/11 ballooning of both jug valves, 07/12 stenting of renal vein, azygos & jug valve ballooning,

At least it kills you, not a life time of slow torture. I have a new look on diseases that you either beat or it kills you so you don't have to think about how you will do it yourself. MS of all the fucking things to get!
I saw this article a week ago and just laughed!

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Had ms for over 19 years now.

Robbie,

Hang in there with the Minocycline. If you have any benefit from it, it may not happen for another 5 months. Please report any effect it has on you, negative or positive. I am curious to know how you do.


Brock

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Here's more info on minocycline and ALS, so don't worry, all of you:

http://www.CPn Help.org/study_finds_minocycline_a

Sarah

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An Itinerary in Light and Shadow Completed Dr Charles Stratton / Dr David Wheldon abx regime for aggressive secondary progressive MS in June 2007, after four years. Still improving with no relapses since starting. Can't run but can paint all day.

I'm not worried about any negative effect of Mino, I am just hoping that it will be effective in delaying or even stopping MS, and perhaps even allow for repair to take place.

Brock