title: Pharmacogenomics of interferon-β in multiple sclerosis: what has been accomplished and how can we ensure future progress?
abstract: Multiple sclerosis (MS) is a progressive disorder of the central nervous system, often resulting in significant disability in early adulthood. The field of pharmacogenomics holds promise in distinguishing responders from non-responders to drug treatment. Most studies on genetic polymorphisms in MS have addressed treatment with interferon-β, yet few findings have been replicated. This review outlines the barriers that currently hinder the validity, reproducibility, and inter-study comparison of pharmacogenomics research as it relates to the use of interferon-β. Notably, statistical power, varying definitions of responder status, varying assay and genotyping methodologies, and anti-interferon-β neutralizing antibodies significantly confound existing data. Future work should focus on addressing these factors in order to optimize interferon-β treatment outcomes in MS.
authors.affiliation: Laboratory of Molecular Cell Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; Neuroscience Research Cluster, Health Sciences Building, University of Saskatchewan, Saskatoon, SK S7K 5E5, Canada.
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Carlson
authors.affiliation: Department of Anatomy and Cell Biology, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; Neuroscience Research Cluster, Health Sciences Building, University of Saskatchewan, Saskatoon, SK S7K 5E5, Canada; Cameco Multiple Sclerosis Neuroscience Research Center, City Hospital, Saskatoon, SK S7K 0M7, Canada.
authors.forename: J Ronald
authors.initials: JR
authors.lastname: Doucette
authors.affiliation: Department of Physical Medicine and Rehabilitation, College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; Cameco Multiple Sclerosis Neuroscience Research Center, City Hospital, Saskatoon, SK S7K 0M7, Canada.
authors.forename: Katherine
authors.initials: K
authors.lastname: Knox
authors.affiliation: Laboratory of Molecular Cell Biology, College of Pharmacy and Nutrition, University of Saskatchewan, Saskatoon, SK S7N 5E5, Canada; Neuroscience Research Cluster, Health Sciences Building, University of Saskatchewan, Saskatoon, SK S7K 5E5, Canada; Cameco Multiple Sclerosis Neuroscience Research Center, City Hospital, Saskatoon, SK S7K 0M7, Canada. Electronic address: aj.nazarali@usask.ca.
authors.forename: Adil J
authors.initials: AJ
authors.lastname: Nazarali
mesh_terms: D057134:Antibodies, Neutralizing / Q000097:blood / Q000276:immunology; D015986:Confounding Factors, Epidemiologic; D005820:Genetic Testing; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D050835:Interferon Regulatory Factors / Q000235:genetics; D016899:Interferon-beta / Q000276:immunology / Q000627:therapeutic use*; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000235:genetics* / Q000276:immunology; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results
chemical_list: D057134:Antibodies, Neutralizing; C431713:IRF5 protein, human; D050835:Interferon Regulatory Factors; D016899:Interferon-beta
keywords: Interferon-β; Multiple sclerosis; Neutralizing antibodies; Pharmacogenomics; Responders