Ass.-Prof. Dr. Matthias Samwald
Leiden University Medical Center, NL
University of Liverpool, UK
Federal Institute for Drugs and Medical Devices, GER
Karolinka Institute, SWE
Golden Helix Foundation, UK
Royal Dutch Pharmacists Association, NL
bio.logis, Center for Human Genetics, GER
St. Antonius Hospital, NL
University of Ljubljana, NL
University Toulouse III Paul Sabatier, FRA
National Cancer Institute, ITA
Uppsala University, SWE
Robert Bosch Hospital Stuttgart, GER
The U-PGx consortium will address major challenges and obstacles for implementation of PGx testing in patient care, taking into account the diversity of healthcare sytems and citizens across Europe. Specifically, U-PGx will investigate if the emerging approach of pre-emptive genotyping of an entire panel of important PGx markers is cost-effective and results in a better outcome for patients. With the pre-emptive PGx testing approach data on multiple important pharmacogenes are collected prospectively and embedded into the patients' electronic record. Typically, it alerts prescribers and pharmacists through electronic clinical decision support systems when a drug is ordered or dispensed for a patient with an at-risk genotype. The new model of personalised medicine through pre-emptive PGx-testing will be conducted at a large scale in seven existing European health care environments (The Netherlands, Spain, UK, Italy, Austria, Greece, Slovenia). upgx.eu
European Union, Horizon 2020, Topic PHC-24-2015: Piloting personalised medicine in health and care systems
Samwald M, XU H, Blagec K, Empey PE, Malone DC, Ahmed SM, Ryan P, Hofer S, and Boyce RD: Incidence of Exposure of Patients in the United States to Multiple Drugs for Which Pharmacogenomic Guidelines Are Available. PLOS ONE 11, no. 10 (October 20, 2016): e0164972.
van der Wouden CH, Swen JJ, Samwald M, Mitropoulou C, Schwab M, and Guchelaar HJ: A Brighter Future for the Implementation of Pharmacogenomic Testing. European Journal of Human Genetics, August 31, 2016
Zhu F, Garcia-Garcia J, Stahl E, et al.: Crowdsourced Assessment of Common Genetic Contribution to Predicting Anti-TNF Treatment Response in Rheumotoid Arthritis. Nature Communications 7 (August 23, 2016): 12460.
Kuch W, Rinner C, Gall W and Samwald M: How Many Patients Could Benefit From Pre-Emptive Pharmacogenomic Testing and Decision Support? A Retrespective Study Based on Nationwide Austrian Claims Data. Studies in Health Technology and Informatics 223 (2016): 253-58.
Blagec K, Romagnoli KM, Boyce RD and Samwald M: Examining Perceptions of the Usefulness and Usability of a Mobile-Based Systems for Pharmacogenomics Clinical Decision Support: A Mixed Methods Study. PeerJ 4 (February 8, 2016):e1671
Rudolf Karch, Martin Bauer, Oliver Langer
Center for Medical Statistics, Informatics, and Intelligent Systems and Department of Clinical Pharmacology
The blood-brain barrier (BBB) protects the brain from potentially harmful substances by preventing their access to the central nervous system (CNS). In addition to the tight junctions between the microvascular endothelial cells and the end-feet of astrocytes, efflux transporters play an important role in protecting the brain from xenobiotic substances. In particular, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP), both located at the apical (blood-facing) membranes of the endothelial cells of brain capillaries, are essential for the function of the BBB. On the other hand, P-gp and BCRP can also impede the entry of potential therapeutics to the brain, e.g., anticancer or antiepileptic drugs.
Molecular imaging techniques, such as positron emission tomography (PET) offer the potential for in vivo measurement of function and density of efflux transporters in health and disease. However, useful interpretation of raw PET imaging data in terms of functional parameters of efflux transporters requires adequate kinetic modeling. Frequently, nonlinear multi-compartment models are necessary to assess the time-course of radiotracers in the brain. Such nonlinear models may lead to substantial uncertainties in various parameter estimates, calling for sophisticated stochastic or Bayesian methods.
EU- 7th framework programme: EURIPIDES - FP7 collaborative project, grant agreement number: 201380 (expired)
FWF SFB F35 Transmembrane Transporters in Health and Disease (see: sfb35.at)
S Zehetmayer, AC Graf, M Posch. Sample size reassessment for a two-stage design controlling the false discovery rate, Stat Appl Genet Mol Biol. 14(5):429-42 (2015)
Martin Bauer, Rudolf Karch, Markus Zeitlinger, Joan Liu, Matthias J Koepp, Marie-Claude Asselin, Sanjay M Sisodiya, Johannes A Hainfellner, Wolfgang Wadsak, Markus Mitterhauser, Markus Müller, Ekaterina Pataraia, Oliver Langer. In vivo P-glycoprotein function before and after epilepsy surgery. Neurology 83:1326-31 (2014)
Martin Bauer, Rudolf Karch, Markus Zeitlinger, Johann Stanek, Cécile Philippe, Wolfgang Wadsak, Markus Mitterhauser, Walter Jäger, Helmuth Haslacher, Markus Müller, Oliver Langer. Interaction of 11C-tariquidar and 11C-elacridar with P-glycoprotein and breast cancer resistance protein at the human blood-brain barrier. J Nucl Med 54(8):1181-1187 (2013)
Julia Müllauer, Rudolf Karch, Jens P. Bankstahl, Marion Bankstahl, Johann Stanek, Thomas Wanek, Severin Mairinger, Markus Müller, Wolfgang Löscher, Oliver Langer, Claudia Kuntner. Assessment of cerebral P-glycoprotein expression and function with PET by combined [11C]inhibitor and [11C]substrate scans in rats. Nucl Med Biol 40(6): 755-763 (2013)
Martin Bauer, Markus Zeitlinger, Rudolf Karch, Peter Matzneller, Johann Stanek, Walter Jäger, Michaela Böhmdorfer, Wolfgang Wadsak, Markus Mitterhauser, Jens P. Bankstahl, Wolfgang Löscher, Matthias Koepp, Claudia Kuntner, Markus Müller, Oliver Langer. Pgp-mediated interaction between (R)-[11C]verapamil and tariquidar at the human blood-brain barrier: a comparison with rat data. Clin Pharmacol Ther 91(2):227-233(2012)
Claudia C Wagner, Marie Simpson, Markus Zeitlinger, Martin Bauer, Rudolf Karch, Aiman Abrahim, Thomas Feurstein, Matthias Schütz, Kurt Kletter, Markus Müller, Graham Lappin, Oliver Langer. A combined accelerator mass spectrometry-positron emission tomography human microdose study with 14C- and 11C-labelled verapamil. Clin Pharmacokin 50(2): 111-20 (2011)
Claudia Kuntner, Jens P. Bankstahl, Marion Bankstahl, Johann Stanek, Thomas Wanek, Gloria Stundner, Rudolf Karch, Rebecca Brauner, Martin Meier, Xiao-Qi Ding, Markus Müller, Wolfgang Löscher, Oliver Langer. Dose-response assessment of tariquidar and elacridar and regional quantification of P-glycoprotein inhibition at the rat blood-brain barrier using (R)-[11C]verapamil PET. Eur J Nucl Med Mol Imaging 37(5):942-53 (2010)
Martin Bauer, Rudolf Karch, Friederike Neumann, Claudia C Wagner, Kurt Kletter, Markus Müller, Wolfgang Löscher, Markus Zeitlinger, Oliver Langer. Assessment of regional differences in tariquidar-induced P-glycoprotein modulation at the human blood-brain barrier. J Cereb Blood Flow Metab 30(3):510-515 (2010)
Claudia C Wagner, Martin Bauer, Rudolf Karch, Thomas Feurstein, Stephan Kopp, Peter Chiba, Kurt Kletter, Wolfgang Löscher, Markus Müller, Markus Zeitlinger, Oliver Langer. A pilot study to assess the efficacy of tariquidar to inhibit P-glycoprotein at the human blood-brain barrier with (R)–11C-verapamil and PET. J Nucl Med 50(12):1954-61 (2009)
Martin Bauer, Rudolf Karch, Friederike Neumann, Aiman Abrahim, Claudia C Wagner, Kurt Kletter, Markus Müller, Markus Zeitlinger, Oliver Langer. Age dependency of cerebral P-gp function measured with (R)-[11C]verapamil and PET. Eur J Clin Pharmacol 65(9):941-6 (2009)
Jens P. Bankstahl, Claudia Kuntner, Aiman Abrahim, Rudolf Karch, Johann Stanek, Thomas Wanek, Wolfgang Wadsak, Kurt Kletter, Markus Müller, Wolfgang Löscher, Oliver Langer. Tariquidar-induced P-glycoprotein inhibition at the rat blood-brain barrier studied with (R)-[11C]verapamil and PET. J Nucl Med 49(8):1328-35 (2008)
Oliver Langer, Martin Bauer, Alexander Hammers, Rudolf Karch, Ekaterina Pataraia, Matthias J. Koepp, Aiman Abrahim, Gert Luurtsema, Martin Brunner, Raute Sunder-Plassmann, Friedrich Zimprich, Christian Joukhadar, Stephan Gentzsch, Robert Dudczak, Kurt Kletter, Markus Müller, Christoph Baumgartner. Pharmacoresistance in epilepsy: a pilot PET study with the P-glycoprotein substrate R-[11C]verapamil. Epilepsia 48(9):1774-84 (2007)
Martin Bauer, Oliver Langer, Peter Dal-Bianco, Rudolf Karch, Martin Brunner, Aiman Abrahim, Rupert Lanzenberger, Andrea Hofmann, Christian Joukhadar, Paolo Carminati, Orlando Ghirardi, Paola Piovesan, Gianluigi Forloni, Mario E. Corrado, Nadège Lods, Robert Dudczak, Eduard Auff, Kurt Kletter, Markus Müller. A PET microdosing study with a potential anti-amyloid drug in healthy volunteers and Alzheimer’s disease patients. Clin Pharmacol Ther 80(3): 216-227 (2006)
Ass.-Prof. Dr. Matthias Samwald
Mayo Clinic, Rochester, MN, USA
University of Pittsburgh, Pittsburgh, PA, USA
Stanford University, Stanford, CA, USA
2013 - 2017
This project aims to improve the ability of clinicians and patients to share pharmacogenomic data and to use it at the point of care. We are creating powerful decisiion support algorithms that assist clinicians in optimizing pharmacotherapy for individual patients based on genetic markers that predict pharmakokinetics and -dynamics. Additionally, we are driving the development of the Medication Safety Code, a standardized barcode that captures data about essential pharmacogenomic markers and drug allergies for an individual patient. This barcode can be easily carried by patients or can be printed on lab reports, and can be interpreted with common smartphones or other devices.
FWF (Austrian Science Fund)
Samwald, M., A. Coulet, I. Huerga, R. L. Powers, J. S. Luciano, R. R. Freimuth, F. Whipple, et al. (2012). "Semantically enabling pharmacogenomic data for the realization of personalized medicine." Pharmacogenomics 13(2): 201-212.
Samwald, M. and K. P. Adlassnig (2013). "Pharmacogenomics in the pocket of every patient? A prototype based on quick response codes." J Am Med Inform Assoc 20(3): 409-412.
Samwald, M., R. Freimuth, J. S. Luciano, S. Lin, R. L. Powers, M. S. Marshall, K. P. Adlassnig, M. Dumontier, and R. D. Boyce. (2013). "An RDF/OWL knowledge base for query answering and decision support in clinical pharmacogenetics." Stud Health Technol Inform 192: 539-542.
Samwald, M. and R. R. Freimuth (2013). "Making data on essential pharmacogenes available for every patient everywhere: the Medicine Safety Code initiative." Pharmacogenomics 14(13): 1529-1531 .