"POLYCIS", polymorphisms of immunosuppressant proteic targets and implication in the drug response in transplantation

• Applicant: Matthias Koitka
• Subject Area: Pharmacology
• Term: from 2009 to 2011
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 132935631

The success of allograft transplantation mainly depends on the clinical use of immunosuppressive drugs (ISD). The ISD therapy is critical due to the risk of under– or overdosage, leading to transplant rejection or major adverse effects, respectively. Dose adjustment guarantees effective and non-toxic blood concentrations. Identifying patients at risk of under-immunosuppression or of adverse effects by their genetic statuses represents certainly the future of Therapeutic Drug Monitoring (TDM) of immunosuppressants. Studies relating genetic factors to ISD effects have not yet been performed systematically. The aims of the present project are to investigate the functional consequences of genetic mutations in the genes encoding proteic targets of ISD using ex vivo approaches and to evaluate their influences on drug efficacy and toxicity in kidney transplant patients. This project will demonstrate that genetic markers of drug response are indeed useful for ISD treatment individualization. Furthermore, our project will deliver all the techniques necessary to carry out future, prospective clinical trials. As an overall goal, we strongly hope that transplant patients will benefit from “personalized medicine” by early genetic testing.

• DFG Programme: Research Fellowships
• International Connection: France
• Host: Professor Dr. Pierre Marquet