Glatiramer Acetate for Multiple Sclerosis (Review)

Department of Neuroscience, Fondazione I.R.C.C.S. - Istituto Neurologico C. Besta, Via Celoria, 11, Milano, Italy, 20133.
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 05/2010; 5(5):CD004678. DOI: 10.1002/14651858.CD004678.pub2
Source: PubMed


This is an updated Cochrane review of the previous version published (Cochrane Database of Systematic Reviews 2004 , Issue 1 . Art. No.: CD004678. DOI: 10.1002/14651858.CD004678)Previous studies have shown that glatiramer acetate (Copaxone (R)), a synthetic amino acid polymer is effective in experimental allergic encephalomyelitis (EAE), and improve the outcome of patients with multiple sclerosis (MS).
To verify the clinical efficacy of glatiramer acetate in the treatment of MS patients with relapsing remitting (RR) and progressive (P) course.
We searched the Cochrane MS Group Trials Register (26 March 2009), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1, 2009), MEDLINE (PubMed) (January 1966 to 26 March 2009), EMBASE (January 1988 to 26 March 2009) and hand searching of symposia reports (1990-2009).
All randomised controlled trials (RCTs) comparing glatiramer acetate and placebo in patients with definite MS, whatever the administration schedule and disease course, were eligible for this review.
Both patients with RR and P MS were analysed. Study protocols were comparable across trials. No major flaws were found in methodological quality. However, efficacy of blinding should be balanced against side effects, including injection-site reactions.
Among 409 retrieved references, we identified 16 RCTs; six of them, published between 1987 and 2007, met the selection criteria and were included in this review. Five hundred and forty RR patients and 1049 PMS contributed to the analysis. In RR MS, a decrease in the mean EDSS score (-0.33 and -0.45), was found respectively at 2 years and 35 months without any significant effect on sustained disease progression. The reduction of mean number of relapse was evident at 1 year (-0.35 ) 2 years (-0.51 ) and 35 months (-0.64), but significant studies ' heterogeneity was found. The number of hospitalisations and steroid courses were significantly reduced. No benefit was shown in P MS patients. No major toxicity was found. The most common systemic adverse event was a transient and self-limiting patterned reaction of flushing, chest tightness, sweating, palpitations, anxiety. Local injection-site reactions were observed in up to a half of patients treated with glatiramer acetate, thus making a blind assessment of outcomes questionable.
Glatiramer acetate did show a partial efficacy in RR MS in term of relapse -related clinical outcomes, without any significant effect on clinical progression of disease measured as sustained disability. The drug is not effective in progressive MS patients.

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    • "lesions is similar to IFN-b, however, GA has somewhat limited effect on disability progression (Rudick et al. 1997; La Mantia et al. 2010). The side effect profile of GA is, however, more favorable and includes local injection site reactions, post injection reaction (flushing, chest tightness, palpitation, and dyspnea within minutes of injection with spontaneous resolution) and rare lipoatrophy with prolonged use. "
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    ABSTRACT: Background Multiple sclerosis is an acquired demyelinating disease of the central nervous system. It is the second most common cause of disability in adults in United States after head trauma.DiscussionThe etiology of MS is probably multifactorial, related to genetic, environmental, and several other factors. The pathogenesis is not fully understood but is believed to involve T-cell-mediated inflammation directed against myelin and other related proteins with a possible role for B cells. The McDonald criteria have been proposed and revised over the years to guide the diagnosis of MS and are based on clinical presentation and magnetic resonance imaging (MRI) of the brain and spinal cord to establish dissemination in time and space. The treatment of MS includes disease modification with immunomodulator drugs and symptom management to address the specific symptoms such as fatigue, spasticity, and pain.Conclusion An update on etiology, pathogenesis, diagnosis, and immunomodulatory treatment of MS is presented.
    Full-text · Article · Jul 2015 · Brain and Behavior
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    • "However, the extent to which these observations can be interpreted as indicative of therapeutic potential is limited because none of those studies showed evidence for restoration of nerve function. Indeed, although progression of disability in relapsingremitting MS may involve effects of chronic demyelination (Dutta and Trapp, 2011), glatiramer acetate has little effect on disability progression in treated patients (La Mantia et al., 2010). Since expression of LINGO-1 is restricted to the CNS, effects of blocking LINGO-1 are unlikely to involve immunomodulation. "
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    ABSTRACT: Blocking LINGO-1 has been shown to enhance remyelination in the rat lysolecithin-induced focal spinal cord demyelination model. We used transcranial magnetic motor-evoked potentials (tcMMEPs) to assess the effect of blocking LINGO-1 on recovery of axonal function in a mouse lysolecithin model at 1, 2 and 4weeks after injury. The role of LINGO-1 was assessed using LINGO-1 knockout (KO) mice and in wild-type mice after intraperitoneal administration of anti-LINGO-1 antagonist monoclonal antibody (mAb3B5). Response rates (at 2 and 4weeks) and amplitudes (at 4weeks) were significantly increased in LINGO-1 KO and mAb3B5-treated mice compared with matched controls. The latency of potentials at 4weeks was significantly shorter in mAb3B5-treated mice compared with controls. Lesion areas in LINGO-1 KO and mAb3B5-treated mice were reduced significantly compared with matched controls. The number of remyelinated axons within the lesions was increased and the G-ratios of the axons were decreased in both LINGO-1 KO and mAb3B5-treated mice compared with matched controls. These data provide morphometric and functional evidence of enhancement of remyelination associated with antagonism of LINGO-1. Copyright © 2015. Published by Elsevier Inc.
    Full-text · Article · Feb 2015 · Experimental Neurology
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    • "GA is approved for the treatment of patients with relapsing–remitting multiple sclerosis (RRMS) and in patients who experience an initial clinical relapse with MRI findings that are compatible with a diagnosis of MS. GA reduces the frequency of disease relapses (La Mantia et al., 2010), and may decrease disease progression. The mechanism of action of GA is still not fully understood. "
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    ABSTRACT: Immune surveillance of the CNS is critical for preventing infections, however there is no accepted experimental model to assess the risk of infection when utilizing disease-modifying agents. We tested two approved agents for patients with multiple sclerosis (MS), glatiramer acetate and fingolimod, in an experimental model of CNS immune surveillance. C57BL/6 mice were infected with the ME49 strain of the neuroinvasive parasite Toxoplasma gondii (T. gondii) and then treated with GA and fingolimod. Neither treatment affected host survival, however differences were observed in parasite load and in leukocyte numbers in the brains of infected animals. Here we demonstrate that this model could be a useful tool for analyzing immune surveillance.
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