Pharmaceutical Technology Europe - April 2010 - (Page 13)

Future research strategies for glucocorticoid therapy Numerous drugs have been developed that target the glucocorticoid receptor (GR); however, recent research on genetic and environmental factors affecting GR signalling indicate that these factors will shape the future of personalised glucocorticoid therapy. The effect of SNPs on GR signalling is likely to be much more complex because GR activation is mediated by a protein complex that consists of numerous proteins, such as heat shock proteins. SNPs in these proteins may also affect cortisol-based drug efficacy. Indeed, SNPs in FKBP5, a protein involved in GR signalling, have been associated with remission in antidepressant treatment. In light of all this research, determining the patient SNP profile of drug targets may have a predictive value for drug efficacy and could form part of the future of personalised medicine. Interestingly, all these factors are associated with reduced GR protein levels, which indicate that individual fluctuation in the amount of drug targets is of relevance for disease and drug therapy. More recently, cell-specific microRNAs, a group of small non-coding RNAs, have been identified as regulators of GR protein levels. Together with classical gene promoter regulation, a complex picture emerges for GR protein expression. Insight into this regulation in patients may be of relevance for individual cortisol-based treatment. targets are also being conducted. One future research strategy could be to use ‘humanised’ animal models. Additionally, I believe that the discovery of microRNAs and RNA-interference technology holds great promise for developing novel therapeutics, which may lead to a new generation of highly specific nucleic acid-based drugs. To deliver such drugs, however, novel carrier tools will also be required. PTE Based on a contribution by Erno Vreugdenhil, Associate Professor at the Leiden/Amsterdam Center for Drug Research, University Leiden (The Netherlands). To read the full version of this article, go to www.pharmtech.com/vreugdenhil www.lacdr.nl Genetic factors Millions of small genetic polymorphisms — single nucleotide polymorphisms (SNPs) — exist between individuals. Several SNPs corresponding with functional domains of the human GR protein and mRNA have already been identified, and follow-up studies have shown that these are associated with the GR’s sensitivity to cortisol. Therefore, mutations in the human GR gene may cause glucocorticoid resistance. Future research strategies Environmental factors It has been known for decades that GR signaling is negatively affected by environmental factors, such as traumatic stress in early life, chronic stress in adulthood and aging. Future strategies are already being seen today; every day, studies are appearing that report diseaseassociated SNPs as important drug targets. Numerous studies focusing on expression regulation of drug 1 CONTENTS 9 THE HUMAN GENOME 2 INTRODUCTION 11 CANCER THERAPY UPDATE 5 MORE THAN SCIENCE NEEDED 14 MANUFACTURING CHALLENGES 7 FUTURE SNP MARKET 16 TOP TECHNOLOGIES http://www.pharmtech.com/vreugdenhil http://www.lacdr.nl

Table of Contents for the Digital Edition of Pharmaceutical Technology Europe - April 2010

Pharmaceutical Technology Europe - April 2010
Table of Contents
Why Personalised Medicine Business Models will Require Long-Term Strategies and Great Flexibility in Order to be Successful
Science Alone Will Not Lead to Better Medicines
The Current and Future Market for SNPs
The Hype, Hope and Reality of Pharmacogenetic Tests
Unraveling the Human Genome
Progress in Molecular Diagnostics
Personalising Cancer Therapy
T Cells for Patient-Specific Cancer Treatments
Future Research Strategies for Glucocorticoid Therapy
Overcoming Manufacturing and Financial Challenges of Personalised Cell Therapies
Public-Private Partnerships Prosper
Eight Latest Technologies Showcased

Pharmaceutical Technology Europe - April 2010