Glatiramer acetate in multiple sclerosis: a review.
Multiple sclerosis (MS) is considered to be primarily an inflammatory autoimmune disease. Over the last 5 years, our view of the pathogenesis of MS has evolved considerably. The axonal damage was recognized as an early event in the disease process and as an important determinant of long-term disability. Therefore, the antiinflammatory and neuroprotective strategies are thought to represent promising approach to the therapy of MS. The therapeutic potential of glatiramer acetate (GA), a synthetic amino acid polymer composed of a mixture of L-glutamic acid, L-lysine, L-alanine, and L-tyrosine in defined proportions, in MS has been apparent for many years. GA has been shown to be effective in preventing and suppressing experimental allergic encephalomyelitis (EAE), the animal model of MS. GA has been, therefore, evaluated in several clinical studies and found to alter the natural history of relapsing-remitting (RR)MS by reducing the relapse rate and affecting disability. These findings were confirmed in open-label follow-up trials covering more than 10 years of treatment. The trials demonstrated sustained efficacy for GA in slowing the progression of disability. The clinical therapeutic effect of GA is consistent with the results of magnetic resonance imaging (MRI) findings from various clinical centers. At a daily standard dose of 20 mg, s.c., GA was generally well tolerated. The induction of GA-reactive T-helper 2-like regulatory suppressor cells is thought to be the main mechanism of the therapeutic action of this drug. In addition, it was recently shown that GA-reactive T cells produce neurotrophic factors (e.g., brain-derived neurotrophic factor [BDNF]) that protect neurons and axons in the area of injury.
Ruggieri
Maddalena
M
Department of Neurological and Psychiatric sciences, University of Bari, Bari, Italy. mruggieri@neurol.uniba.it
Avolio
Carlo
C
Livrea
Paolo
P
Trojano
Maria
M
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D000596:Amino Acids / Q000737:chemistry / Q000627:therapeutic use; D000068717:Glatiramer Acetate; D006801:Humans; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000276:immunology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010455:Peptides / Q000737:chemistry / Q000627:therapeutic use*; D011108:Polymers / Q000737:chemistry
D000276:Adjuvants, Immunologic; D000596:Amino Acids; D018696:Neuroprotective Agents; D010455:Peptides; D011108:Polymers; D000068717:Glatiramer Acetate