Amelioration of experimental colitis by Copaxone is associated with class-II-restricted CD4 immune blocking

Gur, Chamutal; Karussis, D.M.; Golden, Eran; Doron, S.; Ilan, Yaron; Safadi, Rifaat

doi:10.1016/j.clim.2005.10.004

Cited by 14 publications

(11 citation statements)

References 55 publications

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“…Second, it is plausible that an APC-driven Th2 deviation may be pronounced in GA-reactive T cells, as every APC that presents GA should have been in contact with GA and undergone type II differentiation prior to T-cell activation. The concept of an antigen-nonspecific effect of GA is further supported by the fact that GA treatment has been shown to be clinically beneficial in other models of autoimmune or inflammatory conditions, such as arthritis, uveoretinitis, 55 inflammatory bowel disease, 56 and graft rejection. 57 Although T cells might not be the primary target of GA, they are most likely the effector cells of GA-mediated immune modulation.…”

Section: Cross-talk Between Type II Apc and Regulatory Tcell Populationsmentioning

confidence: 99%

Mechanism of Action of Glatiramer Acetate in Treatment of Multiple Sclerosis

2007

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Summary:Glatiramer acetate (GA) (Copolymer-1, Copaxone, Teva, Israel, YEAK) is a polypeptide-based therapy approved for the treatment of relapsing-remitting multiple sclerosis. Most investigations have attributed the immunomodulatory effect of GAs to its capability to alter T-cell differentiation. Specifically, GA treatment is believed to promote development of Th2-polarized GA-reactive CD4 ϩ T-cells, which may dampen neighboring inflammation within the central nervous system. Recent reports indicate that the deficiency in CD4 FoxP3ϩ regulatory Tcells in multiple sclerosis is restored by GA treatment. GA also exerts immunomodulatory activity on antigen presenting cells, which participate in innate immune responses. These new findings represent a plausible explanation for GA-mediated T-cell immune modulation and may provide useful insight for the development of new and more effective treatment options for multiple sclerosis.

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Section: Cross-talk Between Type II Apc and Regulatory Tcell Populationsmentioning

confidence: 99%

Mechanism of Action of Glatiramer Acetate in Treatment of Multiple Sclerosis

2007

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“…The mechanism of the colitis suppression process was identified as being decreased lymphocyte reactivity and decreased secretion of TNF-α, a key mediator of inflammation in MS as well as in other diseases, such as colitis of IBD [3,4,5] and transforming growth factor-β [6]. Copaxone suppressed local mesenteric lymphocyte proliferation and induced a beneficial secretion of transforming growth factor-β [3, 6, 7]. It demonstrated a significant reduction in macroscopic colonic damage, such as preservation of microscopic colonic structure, reduced weight loss and improved long-term survival [3, 6, 7].…”

Section: Discussionmentioning

confidence: 99%

“…Copaxone suppressed local mesenteric lymphocyte proliferation and induced a beneficial secretion of transforming growth factor-β [3, 6, 7]. It demonstrated a significant reduction in macroscopic colonic damage, such as preservation of microscopic colonic structure, reduced weight loss and improved long-term survival [3, 6, 7]. Copaxone modifies the TH1 immune response in MS [3, 6, 7].…”

Section: Discussionmentioning

confidence: 99%

“…It demonstrated a significant reduction in macroscopic colonic damage, such as preservation of microscopic colonic structure, reduced weight loss and improved long-term survival [3, 6, 7]. Copaxone modifies the TH1 immune response in MS [3, 6, 7]. Since Crohn’s disease is also characterized by TH1 predominance, it is reasonable to consider that Copaxone inhibits the inflammation process.…”

Section: Discussionmentioning

confidence: 99%

“…Copaxone also led to amelioration of T-cell proliferation in in vitro studies [3, 6]. Anti-MS drugs (interferon-β 1a and Copaxone) with anti-inflammatory and anti-immune characteristics were shown to be effective in IBD treatment [7,8,9]. Interferon-β 1a was shown to be effective in steroid-refractory active ulcerative colitis [9].…”

Section: Discussionmentioning

confidence: 99%

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Development of Crohn’s Disease in a Patient with Multiple Sclerosis Treated with Copaxone

Charach

Grosskopf

Weintraub³

2008

Digestion

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Background: Copaxone (glatiramer acetate) is a synthetic copolymer mimicking a portion of myelin basic protein, one of several putative autoantigens in multiple sclerosis (MS). Copaxone suppresses the production of tumor necrosis factor (TNF)-α, a key mediator of inflammation in MS as well as in other pathologies, such as colitis of interstitial bowel disease (IBD). Copaxone is a drug approved for the treatment of MS, and one that is very well tolerated with a high safety profile and relatively few side effects. Crohn’s disease has not been associated with its administration. Methods: We describe a patient with MS in remission who had not exhibited any signs of IBD in the past. She had been on Copaxone 20 mg/day treatment for 2 years when she first exhibited gastrointestinal symptoms. Results: Our patient developed Crohn’s disease while on Copaxone treatment as a consequence of long-term immunosuppression. Conclusions: Clinicians should be aware that Crohn’s disease is a potential novel adverse drug effect of Copaxone.

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Glatiramer acetate for treatment of MS: Regulatory B cells join the cast of players

Kaer¹

2011

Experimental Neurology

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Glatiramer acetate (GA, copolymer-1, Copaxone®) is a Food and Drug Administration-approved drug for the treatment of relapsing-remitting multiple sclerosis (MS). However, its mechanism of action remains ill-defined. The available evidence indicates that GA induces antigen-presenting cells with anti-inflammatory properties and promotes the generation of immunoregulatory T cells that suppress pathogenic T cells. A new study by Kala et al. (Exp. Neurol. 2010. 221, 136–145) now shows that B lymphocytes, which are best known for their antibody-secreting properties, contribute to the beneficial effects of GA against experimental autoimmune encephalomyelitis (EAE), the animal model of MS. This commentary discusses these new findings in the context of the pathogenesis of MS and EAE, the emerging immunoregulatory role of B cells in autoimmunity, and the relevance of B cells as targets for immunotherapy in MS.

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Amelioration of experimental colitis by Copaxone is associated with class-II-restricted CD4 immune blocking

Cited by 14 publications

References 55 publications

Mechanism of Action of Glatiramer Acetate in Treatment of Multiple Sclerosis

Mechanism of Action of Glatiramer Acetate in Treatment of Multiple Sclerosis

Development of Crohn’s Disease in a Patient with Multiple Sclerosis Treated with Copaxone

Glatiramer acetate for treatment of MS: Regulatory B cells join the cast of players

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