Dr. Lars Mecklenburg is awarded for his publication entitled "Mesenteritis precedes vasculitis in the rat mesentery after subacute administration of a phosphodiesterase type 4 inhibitor" (1), a compound class being studied as a novel therapy for asthma and chronic obstructive pulmonary disease. In his work, in order to better understand and to investigate the development of arteritis in the splanchnic vasculature of rats, Dr. Mecklenburg describes the results of a time-course study with the compound BYK169171, a selective inhibitor of phosphodiesterase type 4 (PDE4), in rats. His paper describes a new toxicological phenomenon related to the toxicity of PDE4 inhibitors after subchronic treatment in the rats. Dr. Mecklenburg documents the alterations observed in the mesentery by using histology, morphometry, and immunohistology. The adverse effects are precisely described and well documented. The results are appropriately discussed and a postulate about the mechanism of toxicity is formulated. Finally, the relevance of these experimental findings for humans is addressed.

This publication shows in an exemplary way the role and importance of toxicologic pathology in pharmaceutical development where specially designed investigative toxicology studies, the so called non-routine or non-regulatory studies, are of great support to gain deeper knowledge about the mechanism of action of new chemical entities.

Reference:

1. Mecklenburg L, Heuser A, Juengling T, Kohler M, Foell R, Ockert D, Tuch K, Bode G (2006) Mesenteritis precedes vasculitis in the rat mesentery after subacute administration of a phosphodiesterase type 4 inhibitor. Toxicol Lett 163: 54-64

La Grande Motte, France, September 28, 2006

* sponsored by Novartis Pharma AG