Tuesday, 9 February 2016

mimocycline adds nothing to beta interferon to block relapse

Sørensen PS, Sellebjerg F, Lycke J, Färkkilä M, Créange A, Lund CG, Schluep M, Frederiksen JL, Stenager E, Pfleger C, Garde E, Kinnunen E, Marhardt K; RECYCLINE Study Investigators. Minocycline added to subcutaneous interferon β-1a in multiple sclerosis: randomized RECYCLINE study. Eur J Neurol. 2016. doi: 10.1111/ene.12953. [Epub ahead of print]

BACKGROUND AND PURPOSE:Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis(RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) β-1a therapy.
METHODS:This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN β-1a 44 μg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN β-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed.
RESULTS:One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo.
CONCLUSION: Minocycline showed no statistically significant beneficial effect when added to sc IFN β-1a therapy


Some studies have suggested that the anti-biotic minocycline can inhbit microglial activation and so it should be neuroprotective, which it has the potential to be. However, it has been suggested to be immunosupressive too.This is based on some EAE studies. This may be due in some instances be due stressful effects as  mimocycline is very very acidic. So if you do not adjust the pH it is going to be like  hydrocloric acid and will burn your insides and cause stressful effects that control the immune response if you are a mouse. Adjust the PH and it is not much of an immunosuppessive and in this study, this is what was found.  That it was not much of an immunosuppressive so like mouse like man, and could not add any thing to beta interferon. However if it was going to be neuroprotective inhibiting relapses is not what you would be targeting so is it a neuroprotective the jury is still out.

5 comments:

  1. When I read one of ECTRIMS 2015 posters on the use of minocycline for the treatment of CIS, and even though it has neuroprotective activity by inhibiting the cells of the microglia, as is that minocycline is then inserts the possibility of interaction of the intestinal microbiome and MS? (For since it is an antibiotic continued use would destroy the intestinal flora) ...

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  2. MD, I don't understand the point about acidity of minocycline: we have fairly concentrated HCl in the stomach anyway! Also, there are basic amines in the molecule of monocycline; well, I agree - two basic amines per three acidic phenols, but aspirin is a much stronger acid than minocycline, yet it is taken by millions of people (i am not sure if it's taken by mice...). Can you explain?

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    1. This is what MD was referring to.
      https://www.deepdyve.com/lp/wiley/effect-of-minocycline-in-experimental-autoimmune-encephalomyelitis-ZN8GWYf3yg
      This refers to intraperitoneal injection (not oral delivery) when we adjusted the acidity to 7 for the ip injections there was no suppression of disease in our mice.

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    2. The people doing the above study probably didn't read the paper I quoted above from 2002 as its clear that oral monocycline had no effect on disease. One nil to the mouseketeers ;-)

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  3. Thanks mouseketeers, this makes sense

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