Sensitivity to leukemia drugs is predictable
Dr. Wolf-Karsten Hofmann, of the Medical University Clinic III, Frankfurt/Main, was able to show that differences in gene expression are responsible for the different response of patients with acute lymphoblastic leukemia to the drug Imatinib. Thanks to the decoding of the human genome and advances in genetic analysis, the profiles of the genes expressed in the target cells can now be identified and correlated with clinically different phenotypes.
Hofmann applied this method to lymphoblastic leukemia for which the tyrosine kinase inhibitor Imatinib (STI571) represents a novel, highly effective therapeutic option.

However, the majority of patients develop a resistance against this drug within just a few months. In a phase-II study, cells from 19 patients were isolated before or during the treatment with Imatinib and the gene expression was examined through oligonucleotide microarrays. The expression analyses of 95 genes facilitated the distinction of all sensitive cell samples from the resistant ones, thereby demonstrating the precision and meaningfulness of this new diagnostic method.
As the jury emphasized, the results are of considerable clinical relevance for the prognostic assessment of the responder/non-responder status with regard to Imatinib. In addition, they are a pioneering example of the development of individualized therapy via pharmacogenetics and pharmacogenomics.

Cholesterol-independent effects of cholesterol-lowering substances for vascular diseases
Statins have become established in treating disorders of the lipid metabolism. So far, their protective effect on the vascular system has been explained with their favorable impact on the corresponding blood chemistry by inhibiting the hepatic cholesterol synthesis. However, Dr. Ulrich Laufs (Medical Clinic and Outpatient Clinic, Internal Medicine III, University Clinic, Homburg/Saar) discovered cholesterol-independent effects of statins in collaboration with Dr. Matthias Endres (Clinic and Outpatient Clinic for Neurology of the Charité, Humboldt University Berlin) and Dr. Christopher Heeschen (Department for Molecular Cardiology, University Clinic Frankfurt/Main).

Among others, they target the nitrogen monoxide formation in the endothelium. As an important interim step, the physicians identified the inhibition of geranyl geranyl pyrophosphate, which usually reacts with the small protein Rho. Rho, on the other hand, impacts the formation of nitrogen monoxide. Furthermore, the team was able to show on the molecular level that an excess vascular reaction can occur when a patient suddenly stops taking statins - a possibly dangerous rebound phenomenon. Subsequently, the group retrospectively examined 1,616 patients with acute coronary artery constriction and showed that the fact that the patients had ceased to take the statins following their admittance to the hospital did, indeed, increase their cardiovascular risk significantly (PRISM study). It was even higher than for patients who had never taken statins and was independent of the initial cholesterol values. Based on these results, the administration of statins to patients with acute coronary heart disease should not be stopped abruptly. According to the jury, this research contributed to the safe handling of these pharmaceuticals.

The jury
The jury of five consisted of Professor Dr. Walter Lehmacher (Institute for Medical Statistics, Informatics and Epidemiology of the University of Cologne), Professor Dr. Michael P. Manns (Center for Internal Medicine of the Medical School in Hannover), Professor Dr. Stefan C. Meuer (Institute for Immunology of the University of Heidelberg), Professor Dr. Dr. h.c. Peter C. Scriba (Downtown Clinic of the University of Munich) and Professor Dr. Martin Wehling (Clinic of the City of Mannheim, University of Heidelberg). All jury members are proven experts in the field of clinical research.

The Paul Martini Foundation
The non-profit Paul Martini Foundation, Berlin, supports the advancement of pharmaceutical research as well as the research of pharmaceutical therapy and works to expand the scientific dialog about pharmaceutical research and development between medical scientists at universities, hospitals, the research-based pharmaceutical industry, other research institutions and government agencies. The Paul Martini Prize is awarded every year for outstanding achievements in the development of scientific methods for the assessment of clinical pharmacology and therapeutic measures as well as for the advancement of international collaboration in this field.