Disease relevance of Rfwd2

• Most importantly, these novel copolymers suppressed experimental autoimmune encephalomyelitis, induced in the susceptible SJL/J (H-2(s)) strain of mice with the encephalitogenic epitope PLP 139-151, more efficiently than did Cop 1 [1].
• Copolymer 1 (Cop 1, Copaxone [Teva Marion Partners, Kansas City, Missouri, USA]), a random amino acid copolymer of tyrosine (Y), glutamic acid (E), alanine (A), and lysine (K), reduces the frequency of relapses by 30% in relapsing-remitting multiple sclerosis (MS) patients [1].
• Daily administration of Cop-1 is an approved treatment for multiple sclerosis [2].
• Antibody cross-reactivity is here demonstrated between basic protein (BP), the encephalitogenic molecule of myelin, and copolymer 1 (Cop 1), the synthetic amino acid copolymer, which has a suppressive effect on experimental allergic encephalomyelitis and is effective in reducing the number of relapses in exacerbating-remitting multiple sclerosis [3].
• In mice that express the mutant human gene Cu/Zn superoxide dismutase G93A (SOD1), and therefore simulate the chronic human motor neuron disease amyotrophic lateral sclerosis, Cop-1 vaccination prolonged life span compared to untreated matched controls, from 211 +/- 7 days (n = 15) to 263 +/- 8 days (n = 14; P < 0.0001) [2].

High impact information on Rfwd2

• Moreover, YFAK and poly (F, A, K) (FAK) were much more effective than Cop 1 in inhibition of MBP 85-99-specific HLA-DR2-restricted T cell clones [1].
• Cop 1 slows the progression of disability and reduces relapse rate in exacerbating-remitting multiple sclerosis patients [4].
• Therapeutic vaccination with Copaxone (glatiramer acetate, Cop-1) protects motor neurons against acute and chronic degenerative conditions [2].
• In line with the experimentally based concept of protective autoimmunity, these findings suggest that Cop-1 vaccination boosts the local immune response needed to combat destructive self-compounds associated with motor neuron death [2].
• We further showed that the synthetic peptide copolymer 1 (Cop-1), known to suppress experimental autoimmune encephalomyelitis, can be safely substituted for the natural myelin antigen in both passive and active immunization for neuroprotection of the injured optic nerve [5].

Chemical compound and disease context of Rfwd2

• The synthetic amino acid copolymer copolymer 1 (Cop 1) suppresses experimental autoimmune encephalomyelitis (EAE) and is beneficial in multiple sclerosis [6].
• Copolymer 1 [Cop 1, poly(Y,E,A,K)] is a random synthetic amino acid copolymer of L-tyrosine, L-glutamic acid, L-alanine and L-lysine, effective both in suppression of experimental allergic encephalomyelitis and in the treatment of relapsing forms of multiple sclerosis [7].

Biological context of Rfwd2

• The response of all of the Cop 1 specific lines/clones, which were originated in the (SJL/JxBALB/c)F1 hybrids, was restricted to the BALB/c parental haplotype [6].
• Cop 1 binds to various class II major histocompatibility complex (MHC) molecules and inhibits the T cell responses to several myelin antigens [8].
• The responses of all these lines and clones to BP, as followed by both cell proliferation and interleukin 2 secretion assays, were affected by Cop 1 [9].
• In the rat ocular hypertension model, which simulates glaucoma, immunization with Cop-1 significantly reduced the retinal ganglion cell loss from 27.8% +/- 6.8% to 4.3% +/- 1.6%, without affecting the intraocular pressure [5].
• In this study, we tested whether Cop 1 can also hinder the reactivity of host against graft and inhibit graft rejection [10].

Anatomical context of Rfwd2

• Cop 1 exhibited the most extensive and fast binding to antigen-presenting cells [11].
• In addition, several anti-Cop 1 hybridomas cross-reacted with BP [3].
• Adoptively transferred labeled Cop 1-specific suppressor cells were found in brain sections 7 and 10 days after their injection to the periphery, whereas lysozyme-specific cells were absent in the CNS [12].
• In contrast, the number of surviving retinal ganglion cells per square millimeter in glutamate-injected retinas was significantly larger in mice immunized 10 days previously with Cop-1 emulsified in complete Freund's adjuvant than in mice injected with PBS in the same adjuvant (2,133 +/- 270 and 1,329 +/- 121, respectively, mean +/- SEM; P < 0.02) [5].
• Thus, the use of mAbs has uncovered specificities that are not evident in antisera and has revealed pronounced cross-reactivity between BP and Cop 1 at the B-cell level [3].

Associations of Rfwd2 with chemical compounds

• Cycloheximide, a protein synthesis inhibitor, had no effect on the enhanced staining intensity with anti-DR antibody of cells treated with Cop 1 or MBP, whereas it inhibited the enhanced staining of both DR and DQ molecules caused by the respective antibodies, in the absence of these antigens [13].

Regulatory relationships of Rfwd2

• Our findings indicate that the polarization of the Cop 1-induced lines did not result from the immunization vehicle or the in vitro growing conditions, but rather from the tendency of Cop 1 to preferentially induce a Th2 response [6].
• Furthermore, Cop 1 Ts cells ameliorated EAE induced by two unrelated encephalitogenic epitopes of PLP: p139-151 and p178-191, that produced different forms of disease [14].
• In the present study we further investigated the mechanism of Cop 1 suppressive activity and tested whether Cop 1 could inhibit the specific T-cell response to myelin basic protein (BP) [9].

Other interactions of Rfwd2

• Cop 1 inhibited the proliferation of graft-specific T cell lines, as well as their interleukin (IL)-2 and interferon-gamma (IFN-gamma) secretion, when incubated in vitro with the stimulating allogeneic cells [10].
• Specific inhibition of the T-cell response to myelin basic protein by the synthetic copolymer Cop 1 [9].
• BACKGROUND: Copolymer 1 (Cop 1) was previously shown to prevent graft-versus-host disease and interfere in various manifestations of immune rejection [10].
• RESULTS: Cop 1 treatment prolonged skin graft survival and inhibited the functional deterioration of thyroid grafts, in various strain combinations, across minor and major histocompatibility barriers, similarly to the potent immunosuppressive drug FK506 [10].

Analytical, diagnostic and therapeutic context of Rfwd2

• These results suggest that oral administration of Cop 1 may modulate multiple sclerosis as well [15].
• METHODS: Cop 1 was tested in two transplantation systems: skin and thyroid grafting assays [10].
• Oral Cop1 had no effect on collagen-induced arthritis [16].

References