![]() |
|||||||||||
![]() |
Sub theme 4.5
|
Goals of research: general outline |
Donor specific reactivity & nonresponsiveness Manipulation of the immunosystem is necessary for successful clinical organ transplantation. This may be achieved by prescribing immunosuppressive regimen, allowing engraftment, which is traded with debilitating comorbidity associated with aspecific immunosuppression. Success may also be accomplished by tapering the immunosuppresive load allowing the emergence of immunological countermechanisms leading to non responsiveness. In the setting of clinical organ transplantation we study donor specific alloreactivity in an attempt to understand the immunological pathways leading to success or failure. For this purpose it is essential to explore in detail the donor-specific effector, regulatory and memory immune responses in relation to graft acceptance and failure. The identification of immune and non-immune cells with suppressive activities has opened an important new area of cellular immuno therapy and individual immunosuppression. Our specific aim is to find optimal therapeutic strategies for the individual patient. Pharmacotherapy and pharmacogenetics in organ transplantation
Most immunosuppressive drugs are critical dose drugs: they have a narrow therapeutic index. Therapeutic drug monitoring (TDM) is an important tool to optimize immunosuppressive therapy after organ transplantation. Our research focusses on the combination of the following three main topics: Pharmacokinetics (PK): kinetics of immunosuppressive drugs and drug interactions Pharmacodynamics (PD): how to optimize drug therapy after organ transplantation, optimal efficacy with minimal toxicity. New drugs or new drug combinations, sequential regimens. Pharmacogenetics: how do variants in genes encoding for drug-metabolizing enzymes, drug transporters, or drug targets influence PK and PD. Pharmacogenetic research aims to predict clinically important interindividual differences. |
Scientific achievements |
|
Future plans: special goals and approach |
Donor specific reactivity & nonresponsiveness
Studies to further unravel the contributions of effector, memory and regulatory T cells in the anti-donor response in an attempt to identify patients who developed graft acceptance not necessitating full dose immmunosprressive medication and patients who are at risk to reject their allograft. Introduction of new, less toxic and more specific immunosuppressive agents in the transplantation clinic. Furthermore, we aim to exploit mesenchymal stem cell therapy by expanding recipient cells derived at transplantation. Ex vivo generated mesenchymal stem cells might suppress all-reactive effector T cells in organ transplantation. Pharmacotherapy and pharmacogenetics in organ transplantation
Abbreviated AUC or concentrations at time points other than Cmin better reflect overall drug exposure. We aim to perform studies comparing these parameters with traditional TDM to show their true value. The influence of genetic factors on PK/PD will be studied and can then be prospectively used to aid in individual dosing of immunosuppressive drugs in order to reach target concentrations and thus optimize efficacy and avoid side effects. A crucial factor is the need for well-characterized patients who have been uniformly treated and systematically evaluated. To this end we are setting up basic requirements for the collection of genomic DNA from all our future transplant recipients. |
Most recent publications |
|