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Use of pharmacogenomics in clinical trials for multiple sclerosis
Author(s) -
Martin R.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.81.s1.107.x
Subject(s) - multiple sclerosis , glatiramer acetate , medicine , natalizumab , disease , mitoxantrone , remyelination , pharmacogenomics , clinical trial , bioinformatics , expanded disability status scale , immunology , neuroscience , biology , pathology , myelin , central nervous system , chemotherapy
Multiple sclerosis (MS) is a T‐cell mediated autoimmune disease of the central nervous system. Its pathology is characterized by inflammation, demyelination, gliosis and axonal loss. Substantial heterogeneity exists at the levels of genetic susceptibility, clinical presentation and immunological factors as well. While we begin to realize the complexity of multiple sclerosis, it is currently not possible to assess the contributing factors appropriately since biomarkers other than magnetic resonance imaging are lacking. Standard treatment of MS includes interferon‐beta and glatiramer acetate for relapsing–remitting MS. Rapidly progressing and very active disease is treated by conventional immunosuppression with mitoxantrone, cyclophosphamide or other chemotherapeutics, and numerous experimental treatments are currently in testing. Given the complexity of the disease process and its variability between patients, it is no surprise that the response to each of the above treatments is overall modest. Recent developments of large scale gene expression arrays and proteomics approaches allow us to capture many markers and parts of entire biochemical pathways such as apoptosis or proinflammatory responses simultaneously in individual patients. We have begun to employ cDNA or oligonucleotide microarrays to assess the response to the above therapies first in vitro and later, after initiation of treatment, in vivo . These tools will be useful in defining new biomarkers for MS, to gain a better understanding of disease pathogenesis, but particularly also for developing new therapies for MS, identifying responders and nonresponders and rationale combination therapies.