Pharmacogenomics strategies to optimize treatments for multiple sclerosis: Insights from clinical research. (May 2017)

• Record Type: Journal Article
• Authors: Grossman, Iris; Knappertz, Volker; Laifenfeld, Daphna; Ross, Colin; Zeskind, Ben; Kolitz, Sarah; Ladkani, David; Hayardeny, Liat; Loupe, Pippa; Laufer, Ralph; Hayden, Michael
• Is Part Of: Progress in neurobiology. Volume 152(2017:May)
• Page Start: 114
• Page End: 130
• Publication Date: 2017-05
• Subjects: ADRs adverse drug reactions -- APCs antigen-presenting cells -- ARR annualized relapse rate -- CDMS clinically definite MS -- CIS clinically-isolated syndrome -- CTSS Cathepsin S gene -- DMF dimethyl fumarate -- DMT disease-modifying therapies -- EAE experimental autoimmune encephalomyelitis -- GA glatiramer acetate -- GA-DP glatiramer acetate drug product -- GA-RS glatiramer acetate reference standard -- GWAS genome wide association studies -- IFNβ interferon-beta -- IMSGC International Multiple Sclerosis Genetics Consortium -- JVC John Cunningham Virus -- LPS lipopolysaccharide -- MHC major histocompatibility complex -- MMP-9 matrix metaloproteases -- MS multiple sclerosis -- MBP Myelin Basic Protein -- Nabs neutralizing antibodies -- Natco-GA Glatimer manufactured by Natco Pharma Ltd. Hyderabad India -- NARCOMS North American Research Committee on Multiple Sclerosis -- NBCDs non-biological complex drugs -- PBMC peripheral blood mononuclear cells -- PGx pharmacogenomics -- PML Progressive multifocal leukoencephalopathy -- PPMS primary progressive multiple sclerosis -- RMS relapsing multiple sclerosis -- RRMS relapsing remitting multiple sclerosis -- SP secondary progressive -- TRB@ T-cell receptor beta gene (rs71878) -- Th1 myelin-reactive CD4+ T helper cells -- Treg CD4 + CD25 + FoxP3 + regulatory T cells -- VCAM-1 vascular cell adhesion molecule-1; Multiple sclerosis -- Pharmacogenomics -- Personalized medicine -- Glatiramer acetate -- Interferons; Neurobiology -- Periodicals; Neurology -- Periodicals; Neurology -- Periodicals; Neurobiologie -- Périodiques; 612.8
• DOI: 10.1016/j.pneurobio.2016.02.001
• Languages: English
• ISSNs: 0301-0082

Abstract

Highlights: While there are several MS therapies none have been effective in treating all patients. A priori markers to predict the optimal benefit-to-risk profile of an individual MS patient would greatly facilitate the decision-making process, thereby helping the patient receive the most optimal treatment early on in the disease process. Pharmacogenomic methods evaluate how a person's genetic and genomic makeup affects their response to therapeutics. This review focuses on how pharmacogenomics studies conducted from longitudinal clinical studies concerning glatiramer acetate and the interferon products are being used to identify biologically relevant differences in MS treatments and provide characterization of the predictive clinical response patterns. The findings from these pharmacogenomic studies on glatiramer acetate and interferons have provided insights about the prognostic markers associated with MS disease susceptibility and course, as well as the mode of action of MS therapies and characterization of response patterns, both clinically and molecularly. While substantial progress has been made towards the prediction of response to MS therapies, neurologists still do not have reliable means to predict which treatment will best fit specific patients. It is essential that personalized medicine approaches are validated and clinically applied so as to avoid the current trial-and-error paradigm of treatment allocation. Abstract: Multiple sclerosis (MS) is a chronic, progressive, disabling disorder characterized by immune-mediated demyelination, inflammation, and neurodegenerative tissue damage in the central nervous system (CNS), associated with frequent exacerbations and remissions of neurologic symptoms and eventual permanent neurologic disability. While there are several MS therapies that are successful in reducing MS relapses, none have been effective in treating all patients. The specific response of an individual patient to any one of the MS therapies remains largely unpredictable, and physicians and patients are forced to use a trial and error approach when deciding on treatment regimens. A priori markers to predict the optimal benefit-to-risk profile of an individual MS patient would greatly facilitate the decision-making process, thereby helping the patient receive the most optimal treatment early on in the disease process. Pharmacogenomic methods evaluate how a person's genetic and genomic makeup affects their response to therapeutics. This review focuses on how pharmacogenomics studies are being used to identify biologically relevant differences in MS treatments and provide characterization of the predictive clinical response patterns. As pharmacogenomics research is dependent on the availability of longitudinal clinical research, studies concerning glatiramer acetate and the interferon beta products which have the majority of published long term data to date are described in detail. These studies have provided considerable insight in the prognostic markers associated with MS disease and potential predictive markers of safety and beneficial response.