Glatiramer acetate (Copaxone®) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis
We examined the effect of daily subcutaneous injections of GA on antigen-specific T-cell responses in patients with MS. GA appears to function as a universal antigen, inducing primary in vitro proliferation of naive T-cell populations both in patients with MS and in normal healthy controls. Daily subcutaneous injections of GA caused a striking loss of in vitro responsiveness to the GA that was accompanied by immune deviation to a more Th2 type of response. The surviving GA-reactive T cells exhibited a greater degree of degeneracy as measured by cross-reactive responses to combinatorial peptide libraries. GA is, to our knowledge, the first agent effective in the treatment of an autoimmune disease that appears to alter immune function by engagement of the T-cell receptor and may be useful in a variety of autoimmune disorders in which immune deviation to a Th2 type of response may be desirable.
In summary, GA does not appear to have a direct effect on the preexisting memory compartment of T cells, and it does not appear to be selectively cross-reactive with MBP. Instead, GA treatment induces a GA-specific Th2-polarized T-cell repertoire that recognizes antigen in a more degenerate fashion. This may be sufficient to mediate bystander suppression at many sites of inflammation in the CNS of patients with MS, leading to decreased disease activity.
Some doctors are reluctant to start people with more aggressive RRMS on Copaxone, as it seems to take six to nine months to reach full effectiveness.
More Detailed Information on Copaxone
Type of MS and Severity: Copaxone is for relapsing-remitting MS (RRMS).
Effectiveness: Pretty similar to all of the CRABs -- a 29% reduction in annual relapse rate in a two-year trial. However, a 10-year follow-up study seems to indicate that long-term use of Copaxone has very good clinical results. People who stayed on Copaxone for 10 years had an 80% reduction in relapses (in other words, they went from having 1.5 relapses per year to one relapse every 5 years). Comparing people who used Copaxone continuously for 10 years to those who quit after an average of 4.5 years, 91% of the 10-year Copaxone were still walking unaided, versus 50% of the ex-Copaxone users. In addition, only 38% of the long-term Copaxone users demonstrated worsening of disability, versus 72% of those who had quit. It should be mentioned that a large number of people dropped out of this study, so the results could be pretty skewed in favor of Copaxone (as the people who dropped out may have done so because they felt that Copaxone wasn't working).
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