This Is MS - Possible Method of Action for Copaxone Discovered | Unbiased Multiple Sclerosis Research, News, and Community

Copaxone, manufactured by Teva Pharmaceuticals, has long been an alternative for relapsing-remitting multiple sclerosis patients that do not want to take any of the interferon-class of medications such as Avonex, Rebif or Betaseron. While its efficacy has been shown in numerous clinical trials, its mode of action has always been somewhat of a mystery.

A new study sheds some light on what Copaxone might actually be doing to accomplish its beneficial effect. While the particulars of the research go far beyond the complexity any of us will care to delve into, or perhaps even understand, the basic finding are as follows:

Copaxone administration elevates a particular type of immune system cell

These cells are of the CD8+ class, known as the killer T cells for their ability to destroy infected cells

These killer cells, in the presence of Copaxone, regulate the immune system by killing another type of immune system cell known as CD4+

CD4+ cells are usually considered "helper" cells in that they do not actually kill other cells but "help" the rest of the immune system in doing so by, among other things, activating and directing the killer cells

Why the killing of CD4+ cells by CD8+ cells turns out to be a good thing is not quite clear. The immune system is exceedingly complex and any number of theories could be presented, such as that the particular "helper" cells that are killed were the ones directing the attack on the central nervous system. However, what can be deduced is that Copaxone has some immune-system modulating effect that is generally beneficial to MS'ers, and a rising number of at least this particular type of killer cell is not detrimental to an MS'er (at least overall)-- otherwise, Copaxone would have likewise had a negative effect on patients. For so many years, the mantra has been that boosting an MS'ers immune system would be a bad idea... as research continues to unfold the puzzle that is MS, it is become clear that that is not entirely the case.

Click 'read more' for the full abstract

Full Abstract

J Immunol. 2006 Jun 1;176(11):7119-29.

Therapeutic Induction of Regulatory, Cytotoxic CD8+ T Cells in Multiple Sclerosis.

Tennakoon DK, Mehta RS, Ortega SB, Bhoj V, Racke MK, Karandikar NJ.

Department of Pathology.

In the setting of autoimmunity, one of the goals of successful therapeutic immune modulation is the induction of peripheral tolerance, a large part of which is mediated by regulatory/suppressor T cells. In this report, we demonstrate a novel immunomodulatory mechanism by an FDA-approved, exogenous peptide-based therapy that incites an HLA class I-restricted, cytotoxic suppressor CD8(+) T cell response. We have shown previously that treatment of multiple sclerosis (MS) with glatiramer acetate (GA; Copaxone) induces differential up-regulation of GA-reactive CD8(+) T cell responses. We now show that these GA-induced CD8(+) T cells are regulatory/suppressor in nature. Untreated patients show overall deficit in CD8(+) T cell-mediated suppression, compared with healthy subjects. GA therapy significantly enhances this suppressive ability, which is mediated by cell contact-dependent mechanisms. CD8(+) T cells from GA-treated patients and healthy subjects, but not those from untreated patients with MS, exhibit potent, HLA class I-restricted, GA-specific cytotoxicity. We further show that these GA-induced cytotoxic CD8(+) T cells can directly kill CD4(+) T cells in a GA-specific manner. Killing is enhanced by preactivation of target CD4(+) T cells and may depend on presentation of GA through HLA-E. Thus, we demonstrate that GA therapy induces a suppressor/cytotoxic CD8(+) T cell response, which is capable of modulating in vivo immune responses during ongoing therapy. These studies not only explain several prior observations relating to the mechanism of this drug but also provide important insights into the natural immune interplay underlying this human immune-mediated disease.

PMID: 16709875 [PubMed - in process]