title: Pharmacogenomics in neurology: current state and future steps.
abstract: In neurology, as in any other clinical specialty, there is a need to develop treatment strategies that allow stratification of therapies to optimize efficacy and minimize toxicity. Pharmacogenomics is one such method for therapy optimization: it aims to elucidate the relationship between human genome sequence variation and differential drug responses. Approaches have focused on candidate approaches investigating absorption-, distribution-, metabolism, and elimination (ADME)-related genes (pharmacokinetic pathways), and potential drug targets (pharmacodynamic pathways). To date, however, only few genetic variants have been incorporated into clinical algorithms. Unfortunately, a large number of studies have thrown up contradictory results due to a number of deficiencies, including small sample sizes, inadequate phenotyping, and genotyping strategies. Thus, there still exists an urgent need to establish biomarkers that could help to select for patients with an optimal benefit to risk relationship. Here we review recent advances, and limitations, in pharmacogenomics for agents used in neuroimmunology, neurodegenerative diseases, ischemic stroke, epilepsy, and primary headaches. Further work is still required in all of these areas, which really needs to progress on several fronts, including better standardized phenotyping, appropriate sample sizes through multicenter collaborations and judicious use of new technological advances such as genome-wide approaches, next generation sequencing and systems biology. In time, this is likely to lead to improvements in the benefit-harm balance of neurological therapies, cost efficiency, and identification of new drugs.
authors.affiliation: Department of Neurology, St. Josef-Hospital, Ruhr-University Bochum, Germany. andrew.chan@rub.de
authors.forename: Andrew
authors.initials: A
authors.lastname: Chan
authors.forename: Munir
authors.initials: M
authors.lastname: Pirmohamed
authors.forename: Manuel
authors.initials: M
authors.lastname: Comabella
mesh_terms: D002491:Central Nervous System Agents / Q000009:adverse effects / Q000378:metabolism / Q000493:pharmacokinetics / Q000494:pharmacology; D004827:Epilepsy / Q000188:drug therapy; D006261:Headache / Q000188:drug therapy; D006801:Humans; D019636:Neurodegenerative Diseases / Q000188:drug therapy; D009462:Neurology / Q000379:methods / Q000639:trends*; D010597:Pharmacogenetics / Q000379:methods / Q000639:trends*; D010599:Pharmacokinetics; D010641:Phenotype; D020521:Stroke / Q000188:drug therapy
chemical_list: D002491:Central Nervous System Agents