E X P E R T O P I N I O N Glatiramer acetate in the treatment of multiple sclerosis Alex Tselis Omar Khan Robert P Lisak Division of Neuroimmunology, Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA Correspondence:Alex Tselis Department of Neurology UHC-8D, Wayne State University School of Medicine, 4201 St Antoine St, Detroit, MI 48201, USA Tel +1 313 745 4268 Fax +1 313 745 4216 Email atselis@med.wayne.edu Abstract: Glatiramer acetate is an immunomodulating drug used in the treatment of multiple sclerosis. It consists of a copolymer of amino acid residues in the same stoichiometric propor- tions as in myelin basic protein. Its mechanism of action is not entirely known and is probably multifaceted, with deletion of some immune cell populations and stimulation of others in these patients. Some mechanisms involve neuroprotectant effects. There is ample evidence of its efﬁcacy in relapsing-remitting disease, using both clinical and imaging measures of disease activity, and in this paper we review the clinical and basic studies of this drug. Finally we discuss how some of its neuroprotectant effects may be useful in neurodegeneration such as is seen in more advanced cases of multiple sclerosis and other diseases such as amyotrophic lateral sclerosis and Parkinson’s disease. Keywords: glatiramer acetate, multiple sclerosis, neurodegeneration Introduction Multiple sclerosis (MS) is an inﬂammatory demyelinating disease of the central nervous system (CNS), affecting separate regions of the brain and spinal cord at different times, with axonal damage. It is usually relapsing and remitting (RRMS), at least initially. The disease often enters a secondary progressive (SPMS) phase, with smoothly increasing deﬁcits, leading to substantial disability over time. In this phase of the disease, the pathogenesis is more “degenerative” than inﬂammatory. It must be acknowledged that this is an oversimpliﬁcation and depends on deﬁning the inﬂammatory phase of RRMS as gadolinium enhancement of lesions on magnetic resonance imaging (MRI) T1 sequences, a marker of changes in the blood-brain barrier to humoral factors. Thus the lack of gadolinium enhancement would not rule out inﬁltration of inﬂammatory cells and it is known that using triple dose of gadolinium shows that many lesions thought not to enhance with a single dose still have blood-brain barrier defects. In addition the persistence of cerebrospinal ﬂuid (CSF) oligoclonal bands and the detection of inﬂammatory cells in the brain and spinal cord of SPMS patients, in the absence of gadolinium enhancement, further supports a persistence of the inﬂammatory component in the pathogenesis of MS lesions even during the “degenerative” phase of the course of the disease. A small proportion of cases are progressive at onset, and this is known as the primary progressive form of MS (PPMS). The term “chronic progressive” MS (CPMS) is an obsolete term encompassing SPMS, PPMS, and progressive relapsing MS (PRMS). More recently it has become clear that there are extensive changes in the gray matter including cerebral cortex and deep nuclear structures such as the thalamus and that these changes occur very early in the course of the disease. The mechanisms of these neuronal changes are not well understood and there are likely several of importance. Moreover the relationships between the pathogenic processes in white Neuropsychiatric Disease and Treatment 2007:3(2) 259–267 © 2007 Dove Medical Press Limited.All rights reserved 259