* Copaxone, copolymer-1
It has always irritated me, this substance. It consists of four amino-acids (l-alanine, l-glutamic acid, l-lysine, and l-tyrosine, the four most frequent found in myelin oligodendrocyte glycoprotein [MOG] in defined weigth-relation but random order. These are but some of the potential antigens to the activated allogenic CD4+ T lymphocytes believed to act in an autoimmune action – with all uncertainties related to this claim . It is cooked together in a random fashion, meaning that no molecule resambles the next, and is extremely expensive for its simplicity. According to its preliminary conception, the mixture should induce tolerance to the antigens, later other effects have been suggested [recent examples among many others: 2,7].
And still, it seems to work. It was licenced for therapy in the US in 1996 and an open study performed on the previously randomised patients showed a sustained effect even after 6 years [3,4]. For a long time, I have ignored this substance which was also tested in patients of a much lower EDSS than the simultaneous studies of the beta-interferons. However, informing of quite other relapse rates in a placebo-maniac study as measure of clinical effect – at least showing how uncertain a measure this parameter is, - Khan et al.  found it as effective as IFN-1B (high-dose IFN-1A was not tested). Although some controversies exist , I am slowly believing that this substance might work – the question remains, however, why it works and what else might on a similar simple basis be of benefit for MS-patients. Could it simply be an unspecific, immune-stimulating (irritating) effect, which might as well be attributed to a numer of other therapeutic approaches (e.g., an unspecific monthly load of intravenous immuneglobulin-G, IVIG)?. But also stimulating for my continued resistance towards this approach is the question, what can all be claimed to work in MS – even when based on controlled studies.
As can be seen, the mixture profits from deeper believers
than me, and they can speak for themselves (and probably possess more effective
media for doing so). Anyhow, the treatment of MS remains an open case,
in which too much agreement is a damage of its own. Having said so, I shall
not exclude that the future might offer more detailed information on this
1. Ben-Nun A, Mendel I, Bakimer R, Fridkis-Hareli
M, Teitelbaum D, Arnon R, Sela M, Kerlero de Rosbo N. The autoimmune reactivity
to myelin oligodendrocyte glycoprotein (MOG) in multiple sclerosis is potentially
pathogenic: effect of copolymer 1 on MOG-induced disease. J Neurol 1996;243(Suppl
2. Li QQ, Bever CT. Glatiramer acetate blocks interleukin-1-dependent nuclear factor-kappaB activation and RANTES expression in human U-251 MG astroglial cells. Brain Res Mol Brain Res 2001;87:48-60.
3. Karni A. Bakimer-Kleiner R. Abramsky O. Ben-Nun A. Elevated levels of antibody to myelin oligodendrocyte glycoprotein is not specific for patients with multiple sclerosis. Arch Neurol 1999;56:311-5.
4. Johnson KP; Brooks BR; Ford CC; Goodman A, Guarnaccia J; Lisak RP; Myers LW; Panitch HS; Pruitt A; Rose JW, Kachuck N; Wolinsky JS. Sustained clinical benefits of glatiramer acetate in relapsing multiple sclerosis patients observed for 6 years. Copolymer 1 Multiple Sclerosis Study Group. Mult Scler 2000;6:255-66.
5. Khan OA, Tselis AC, Kamholz JA, Garbern JY, Lewis RA, Lisak RP. A prospective, open-label treatment trial to compare the effect of IFN beta-1a (Avonex), IFNbeta-1b (Betaseron), and glatiramer acetate (Copaxone) on the relapse rate in relapsing-remitting multiple sclerosis. : Eur J Neurol 2001;8:141-148.
6. Weinstein A. Schwid SI. Schiffer RB. McDermott MP. Giang DW. Goodman AD. Neuropsychologic status in multiple sclerosis after treatment with glatiramer. Arch Neurol 1999;56:319-24.
7. Fridkis-Hareli M, Neveu JM, Robinson RA, Lane WS, Gauthier L, Wucherpfennig KW, Sela M, Strominger JL. Binding motifs of copolymer 1 to multiple sclerosis- and rheumatoid arthritis-associated HLA-DR molecules. J Immunol 1999;162:4697-704.
Inserted September 21, 2001
Revised January 25, 2002