Pharmacogenomics of Multiple Sclerosis: Current Status and Potential Applications

Masaaki      Niino; Seiji      Kikuchi

Abstract

In the past decade, treatment for multiple sclerosis (MS), especially with respect to disease modifying therapies (DMTs), has substantially improved. Responses to DMTs, such as interferon β and glatiramer acetate, are not uniform, with considerable variability seen in efficacy and toxicity. Furthermore, unexpected serious side effects have been reported for recently developed therapies. There are currently no reliable markers for the interindividual differences in drug response prior to the initiation of therapy for MS. It would therefore be profoundly useful if we could apply genomic based personalized therapy to MS patients. Here, we review the current literature on the pharmacogenomics of MS and discuss the future application of pharmacogenomics as a potential guide for clinical decision making.

Keywords: Genomics and personalized medicine, multiple sclerosis, pharmacogenetics, pharmacogenomics, therapeutics, multiple sclerosis (MS), disease modifying therapies (DMTs), toxicity, interferon (IFN), intramuscular (IM), subcutaneous (SC), glatiramer acetate (GA), magnetic resonance imaging (MRI), expanded disability status scale (EDSS), fluid attenuated inversion recovery (FLAIR), relapsing-remitting MS (RRMS), genome-wide association study (GWAS), glucocorticoid (GC), IFN, tyrosine kinase 2 (TYK2), Janus kinase 1 (JAK1), IFN-stimulated response element (ISRE), cathepsin S (CTSS), myxovirus resistance A (MXA), human leukocyte antigen (HLA), IL10RBguanylate binding protein 1(GBP1), hyaluronan proteoglycan link protein 1 (HAPLN1), calpastatin (CAST), Mini-Lymphochip (MLC), T-cell receptor (TCRB), Citron, Collagen type XXV 1, Cathepsin S, Glutamate receptor, ionotropic, AMPA 3, Hyaluronan proteoglycan link protein 1, Janus kinase 1, Mini-Lymphochip, Myxovirus resistance A, Neuronal PAS domain protein 3, Progressive multifocal leukoencephalopathy, Relapsing/remitting multiple sclerosis, Single-nucleotide polymorphism, Steroidogenic acute regulatory gene, –, related lipid transfer domain, containing 13, Tumor necrosis factor (ligand) superfamily, member 10, United Europeans for the development of pharmacogenomics in MS, Zinc finger and autoimmune thyroid hook domain, containing