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Public release date: 16-Mar-2006
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Contact: Brooke Grindlinger
press_releases@the-jci.org
212-342-9006
Journal of Clinical Investigation

Combining multiple treatments improves multiple sclerosis therapy
Multiple sclerosis (MS) is an inflammatory autoimmune disease of the central nervous system (CNS) in which white blood cells known as lymphocytes attack the myelin insulation on nerves in the spinal cord and brain. Glatiramer acetate (GA) is a drug currently approved for MS treatment, but new therapies are needed to improve effectiveness and reduce side effects. Now, in a study appearing online on March 16 in advance of print publication in the April issue of the Journal of Clinical Investigation, Scott S. Zamvil and colleagues at the University of California, San Francisco, show that treating MS with combinations of immune modulating drugs can greatly reduce MS disease. The researchers treated the "EAE mouse" model of MS with GA in combination with atorvastatin (Lipitor), a cholesterol-lowering drug shown to improve MS symptoms in clinical trials. Compared to EAE animals treated with either drug alone (which had no effect on established MS), EAE mice receiving the combination therapy demonstrated a significant prevention and reversal of clinical MS severity, with less myelin loss, CNS inflammation, and MS disease incidence. The authors then treated isolated inflammatory cells called macrophages with these drugs and found that the combination therapy mediated its effects by promoting the secretion of the anti-inflammatory molecule IL-10 and suppressed production of the proinflammatory molecules IL-12 and TNF-alpha. Importantly, the combined drug therapy utilized doses of each drug that were lower than the doses used in the single drug treatment method. These data suggest that combined delivery of drugs which act through different mechanisms may enhance the therapeutic efficacy of MS and reduce the negative side effects that result from treatment strategies which use the single drug delivery approach.

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TITLE: Immunomodulatory synergy by combination of atorvastatin and glatiramer acetate in treatment of CNS autoimmunity

AUTHOR CONTACT:

Scott S. Zamvil
University of California, San Francisco, California, USA
Phone: (415) 502-7395; Fax: (415) 502-8512; E-mail: zamvil@ucsf.neuroimmunol.org

View the PDF of this article at: https://www.the-jci.org/article.php?id=25805

http://www.eurekalert.org/pub_releases/ ... 031006.php

This is good news! However, I'm confused about one thing...

Compared to EAE animals treated with either drug alone (which had no effect on established MS), EAE mice receiving the combination therapy demonstrated a significant prevention and reversal of clinical MS severity, with less myelin loss, CNS inflammation, and MS disease incidence.

This seems to be contradictory to information elsewhere in the news release as it seems to be saying that neither copaxone nor atorvastatin have an effect on "established MS." Is it just me, or is anyone else confused by this?

NHE

NHE,

For what it is worth, here is what I am seeing lately with all of this newer data coming forth.

The key word in that sentence is "established" MS. If you watch and read closely, you will find that there is more concentration now on treating "probable MS" and CIS (clinically isolated syndrome) to try to keep the patient from developing full-blown MS.

So, even though it appears contradictory, I don't believe it really is. In "most" cases, referring to "established" MS may indeed refer to patients who have had MS many years and already are on the EDSS scale, or who are now SPMS, etc. And we do know that unfortunately, there isn't much that can claim remarkable results when taken late in the progress of the disease.

But, research is allegedly beginning to show that if taken much EARLIER, sometimes BEFORE MS is diagnosed as a "definite", then combination treatment can produce "significant prevention and reversal of clinical MS severity, with less myelin loss, CNS inflammation, and MS disease incidence."

In order to prevent MS disease "incidence", a patient logically must be pre-definite MS diagnosis.

As I said, these articles go along with many others in which data is allegedly indicating that the EARLIER in the disease process (even before definite diagnosis) the treatment is started, the better the results.

Deb

Ok............I also read very closely the actual study article.

What they did was test "sub-optimal" doses of the combination of the two drugs, just to see if it would be worth following up on.

They did test the combination on EAE mice, but once again, according to the overall focus of this study, the mice did have early EAE. The main focus of the study itself was actually to see if those two particular drugs interacted with each other or was possibly synergistic. They established they were likely synergistic and why they were.

The press article itself IS a tad bit misleading, as this study appears to be mainly for the purpose of laying some initial groundwork to receive funding to go further with more study and eventually possibly future actual clinical trials to attempt to determine if and how the combination may or may not be helpful for MS, and at what stages of MS.

It is a VERY early study.

Deb

Melody,

I see that your husband is taking Lipitor in conjunction with Copaxone. Have you noticed a difference since starting Lipitor? I'm currently taking Copaxone and was considering adding Lipitor to my regimen. Also, how did your husband get a prescription for it? Thanks.

Multiple Sclerosis Drug Combined with Lipitor May Stop or Reverse Disease - Dosages Cut in Half with Fewer Negative Side Effects
March 16th 2006



Lipitor


Combining treatments may improve outcomes for patients with Multiple Sclerosis (MS), according to research done on mice and published online by the Journal of Clinical Investigation. Scott S. Zamvil and colleagues at the University of California, San Francisco found that mice treated with a combination of Glatiramer acetate (GA) and atorvastatin (Lipitor) demonstrated “a significant prevention and reversal of clinical MS severity” of MS symptoms.

Lipitor is a cholesterol lowering drug that has previously been shown to improve MS symptoms. Glatiramer acetate (Teva Pharmaceutical Industries Ltd.'s Copaxone) is a drug currently approved for MS treatment. The researchers found that treating MS with combinations of immune modulating drugs can greatly reduce MS disease.

According to the researchers, treating EAE (experimental autoimmune encephalomyelitis) mice with the combination therapy caused the animals to lose less myelin, prevented CNS inflammation, and MS disease incidence.



The researchers then treated isolated inflammatory cells called macrophages with these drugs and found that the combination therapy mediated its effects by promoting the secretion of the anti-inflammatory molecule IL-10 and suppressed production of the proinflammatory molecules IL-12 and TNF-alpha.

The researchers believe that the combined delivery of drugs, which act through different mechanisms, may enhance the therapeutic efficacy of MS and reduce the negative side effects. Also the drug dosages were less than the dosages used in regular single drug treatments.



Copaxone has been shown to be 30 to 35 percent effective alone. According to Bloomberg News, all MS drugs have to be injected, and have “severe side effects”. None of the MS drugs are very potent.

Lipitor on the other hand can be taken orally and is considered relatively safe. Lipitor, the best selling drug in the world, appears to block production of immune system agents, called cytokines, involved in the disease process. Currently the University of California, San Francisco is looking for 152 patients at 14 hospitals to participate in clinical trials. These trials will investigate the effect Lipitor alone has on MS. Contact the office of Scott Zamvil, associate professor of neurology at University of California, San Francisco, for more information.



There are 400,000 MS sufferers in the US. The illness causes neurological symptoms that include loss of motor control, blindness and temporary recurring paralysis. The condition occur when the body’s natural defenses are over stimulated and begin stripping the protective insulation, called myelin, from nerve fibers in the central nervous system, which includes the brain, optic nerves and spinal cord.

http://www.bestsyndication.com/Articles ... atment.htm

Dunmann wrote:Melody,

I see that your husband is taking Lipitor in conjunction with Copaxone. Have you noticed a difference since starting Lipitor? I'm currently taking Copaxone and was considering adding Lipitor to my regimen. Also, how did your husband get a prescription for it? Thanks.

I can't say if Lipitor helped it might have but John's improvements happened just prior to starting copaxone in July 2005. He all of a sudden took a turn back to normal in June of 2005. We have not had an official relapse since although we have had to scares this winter that fiddling with his dosages of Vitamin D3, lipitor, turmeric, glucosamine and vitamin C might have pulled him out of. I just don't know. Sorry this appears to not be of much help but it's the best answer I can give.