Interferon Beta 1-A + Doxycycline

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Interferon Beta 1-A + Doxycycline

Postby bromley » Mon Dec 10, 2007 3:39 am

Combination Therapy With Interferon Beta-1a and Doxycycline in Multiple Sclerosis 10 December 2007

A preliminary study suggests that combining a medication currently used to treat multiple sclerosis with an antibiotic may slow the progress of the disease, according to an article posted online today that will appear in the February 2008 print issue of Archives of Neurology, one of the JAMA/Archives journals.

“Multiple sclerosis (MS) is an immune-mediated disorder that affects genetically susceptible individuals after exposure to certain, as yet unidentified environmental antigens,” or disease-causing agents, the authors write as background information in the article. The development of MS involves inflammation that destroys parts of the brain along with progressive degeneration of brain tissue. The most common type is relapsing remitting MS, in which patients experience attacks of symptoms such as muscle weakness and spasms followed by periods of symptom-free remission. Many patients with relapsing-remitting MS who take interferon, a medication that boosts the immune system and fights viruses, still experience relapses and may continue to develop new areas of damaged brain tissue (lesions) visible on magnetic resonance imaging (MRI).

Alireza Minagar, M.D., of Louisiana State University Health Sciences Center, Shreveport, and colleagues conducted a single-center trial involving 15 patients (average age 44.5) with relapsing-remitting MS who had been taking interferon for at least six months and were experiencing symptoms and developing new brain lesions. For four months, participants took 100 milligrams daily of the antibiotic doxycycline in addition to continuing interferon therapy. They underwent monthly neurological examinations, MRI to detect brain lesions and blood work to monitor safety.

After four months, the combination treatment resulted in fewer lesions visible on MRI—60 percent of the patients had more than a one-fourth reduction in the number of lesions from the beginning of the study. The patients also had reduced average scores on a scale designed to assess disability levels. Only one patient relapsed; adverse effects were mild and included only known effects of the two drugs individually rather than new effects associated with combining the medications.

Antibiotics in the tetracycline family, including doxycycline, may be effective against MS and other inflammatory diseases by inhibiting the action of enzymes that destroy certain nervous system cells, protecting the brain and increasing the effectiveness of the immune system, the authors note.

“There is growing interest in combination therapy in patients with MS to stabilize the clinical course, reduce the rate of clinical relapses and decelerate the progressive course of the underlying pathologic mechanism,” they write. “Overall, data from this cohort suggest that the treatment combination of oral doxycycline and interferon beta-1a may be safe and effective in some patients with MS; however, further controlled clinical trials are warranted to demonstrate safety and efficacy in a larger patient population.”

Abstract



Objective: To evaluate the efficacy, safety, and tolerability of combination therapy with intramuscular interferon beta-1a and oral doxycycline, a potent inhibitor of matrix metalloproteinases, in patients with relapsing remitting multiple sclerosis (RRMS) having breakthrough disease activity.

Design: Open-label, 7-month trial.

Setting: Louisiana State University Health Sciences Center, Shreveport.

Patients: Fifteen patients with RRMS taking interferon beta-1a with breakthrough disease activity took doxycycline for 4 months. Patients underwent monthly neurologic examination,magnetic resonance imaging of the brain using triple-dose gadolinium, and safety blood work.

Interventions: Ongoing treatment with intramuscular interferon beta-1a plus oral doxycycline, 100 mg daily, for 4 months.

Main Outcome Measures: The primary end point was gadolinium-enhancing lesion number change, and the secondary end points were relapse rates, safety and tolerability of the combination of interferon beta-1a and doxycycline in patients with MS, Expanded Disability Status Scale score, serum matrix metalloproteinase-9 levels, and transendothelial migration of monocytes exposed to serum from patients with RRMS.

Results: Combination of doxycycline and interferon beta-1a treatment resulted in reductions in contrastenhancing lesion numbers and posttreatment Expanded Disability Status Scale values (P.001 for both).Only 1 patient relapsed. Multivariate analyses indicated correlations between decreased serum matrix metalloproteinase-9 levels and enhancing lesion activity reduction. Transendothelial migration of monocytes incubated with serum from patients with RRMS undergoing combination therapy was suppressed. Adverse effects were mild; no adverse synergistic effects of combination therapy or unexpected adverse events were reported.

Conclusions: Combination of intramuscular interferon beta-1a and oral doxycycline treatment was effective, safe, and well tolerated. Controlled clinical trials in larger cohorts of patients with MS are needed to evaluate the efficacy and tolerability of this combination.

Source: Arch Neurol. 2008;65(2):(doi:10.1001/archneurol.2007.41) ©2008 American Medical Association. All rights reserved.(10/12/07)
Last edited by bromley on Mon Dec 10, 2007 5:11 am, edited 1 time in total.
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Postby CureOrBust » Mon Dec 10, 2007 4:44 am

I am sure I have also heard of something similar with mino. Does anyone know of any comparisons / scientific best guesses over the comparison between doxy and minocycline?
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Postby bil » Mon Dec 10, 2007 8:27 am

CureOrBust wrote:I am sure I have also heard of something similar with mino. Does anyone know of any comparisons / scientific best guesses over the comparison between doxy and minocycline?


If I remember correctly there was a study (I think in-vitro and mice) comparing the neuroprotective effects of 4 members of the tetracycline family. Minocycline was the most effective, Doxycycline 2nd. I'll try and find a link for it.
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Postby bil » Mon Dec 10, 2007 8:32 am

bil wrote:
CureOrBust wrote:I am sure I have also heard of something similar with mino. Does anyone know of any comparisons / scientific best guesses over the comparison between doxy and minocycline?


If I remember correctly there was a study (I think in-vitro and mice) comparing the neuroprotective effects of 4 members of the tetracycline family. Minocycline was the most effective, Doxycycline 2nd. I'll try and find a link for it.


I think it might have been this - kindly provided by Anectode when I asked a similar question :

http://www.pnas.org/cgi/content/full/95/26/15769
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Neuroprotection: Mino vs Doxy

Postby Shayk » Mon Dec 10, 2007 8:18 pm

CureO

This abstract doesn’t give any details but again from the vantage point of neuroprotection it gives the impression mino might be better than doxy.

Neuroprotection by tetracyclines
Recent findings have provided novel insights into the molecular and cellular mechanisms of protection of neurons and oligodendrocytes by tetracyclines. These advances have prompted several clinical trials with minocycline, the most effective tetracycline which are still in their early phases. Thus, tetracyclines hold great promise as therapeutic agents for the treatment of human neurodegenerative diseases.

An example specific to MS (scientific best guesses)--some suggest excess Ca might contribute to axonal injury.

Neuronal injury in multiple sclerosis
The precise mechanisms of axonal loss are poorly understood, and three hypotheses have been proposed: 1) The damage is caused by an inflammatory process, 2) There is an excessive accumulation of intra-axonal Ca2+, 3) Demyelinated axons undergo degeneration due to lack of trophic support by myelin, or myelin forming cells.

General Mechanisms of Axonal Damage and Its Prevention
The precise mechanisms of axonopathy are poorly understood, but likely involve excess accumulation of Ca ions.

The good news—mino just might help counter-act the excess Ca.

Neuroprotectant minocycline depresses glutamatergic neurotransmission and Ca(2+) signalling in hippocampal neurons
This pharmacological profile suggests that the neuroprotective effects of minocycline might be associated with the mitigation of neuronal excitability, glutamate release, and Ca(2+) overloading.

I don’t know if doxy has the same "profile", but if you search mino and neuroprotection on Pub Med you get lots of hits, I only got two hits when I searched doxy and neuroprotection.

Take care....

Sharon
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Postby CureOrBust » Tue Dec 11, 2007 12:58 am

thanks all.
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Postby bromley » Tue Dec 11, 2007 2:36 am

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Postby gwa » Tue Dec 11, 2007 5:43 am

bromley,

Did you leave out the last part of the article on purpose?? Sarah will clobber you, and good for her!


"Helen Yates, of the MS Resource Centre, said the condition was complex and difficult.

She said other work was examining the possibility that MS was linked to an infection of the bacterium Chlamydia pneumoniae - more commonly associated with respiratory disease - in the brain


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Postby bromley » Tue Dec 11, 2007 7:14 am

GWA,

You're going bonkers GWA. The BBC article includes the quote you mention. Perhaps abx are messing with your thinking?

Ian

PS I've heard that chocolates and CPn don't mix so I won't be sending you any more of the former.
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Postby gwa » Tue Dec 11, 2007 7:40 am

bromley,

You are right! No more booze for me before breakfast.

gwa
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Postby robbie » Tue Dec 11, 2007 7:45 am

She said other work was examining the possibility that MS was linked to an infection of the bacterium Chlamydia pneumoniae - more commonly associated with respiratory disease - in the brain


Is this the first time that cpn has been considered in ms, Are they just discovering this now after all the other research. When they diagnose ms they eliminate all other possibilities, why not add this to the list. I just can't belive there are researchers around the world doing there thing as complicated as it is and theres one of them saying hey instead of supressing or eliminating the immune system what about just taking some doxycycline, sorry to the millions of ms suffers that thought we were on the right track, theres just no f!@#ing way.
Had ms for over 19 years now.
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Postby viper498 » Tue Dec 11, 2007 8:23 am

Robbie,

Why not? Why assume that all of the other researchers are right, and the one that is recommending ABX is wrong? The majority isn't producing anything that is helping people are they?

Remember when stomach ulcers used to be caused only by stress and heartburn? They called the researcher crazy, who said it was caused by bacteria.

You should not have stopped taking your ABX in my opinion. I would have given it 6 months to a year...
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Postby robbie » Tue Dec 11, 2007 8:37 am

When someone dies with ms do they not check the brain to see if it had an infection? Would this not show up? there must be many ms brain biopsies, is there alot of cpn found?
Had ms for over 19 years now.
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Postby Loriyas » Tue Dec 11, 2007 10:38 am

I have to agree with Brock. It seems to me that researchers have gone down one path based on one theory. It just seems to build on that.
What if they would go down another path and would find something totally different? I don't know which path is correct or if there are actually many paths (different medications work for different people) But I would think the broader the research the better at this point. After all, the autoimmune path isn't giving us all the answers now. Maybe the answers are actually somewhere else. I hope so.
Lori

BTW Robbie, would you reconsider the minocycline? If it isn't causing you any bad side effects what's the harm? And if you give it more time and perhaps add the other antibiotics you will know for sure if it works or doesn't. Just a thought!
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Postby Lyon » Tue Dec 11, 2007 12:02 pm

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Last edited by Lyon on Thu Dec 01, 2011 1:42 pm, edited 1 time in total.
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