Gerd Bode
University of Gottingen, Germany
Title: The utility of the minipig as an animal model in regulatory toxicology
Biography
Biography: Gerd Bode
Abstract
Gratitude is within the ethical tradition of Japanese towards experimental animals, because these provide valuable data for efficacy and safety of pharmaceutical compounds before fi rst administration to humans. Researchers must therefore develop strict responsibilities to use these models under strict adherence to the 3Rs (Refi ne, Reduce, Replace). Models should be relevant; and a relevant model is an animal which expresses receptors/epitopes like humans, reveals comparable pharmacodynamic eff ects and resembles humans in regard to kinetic parameters like metabolism, exposure levels, protein
binding and bioavailability. For primary or secondary pharmacodynamics, next to traditional species, also transgenic or disease models are being used, but for non-clinical safety studies predominantly traditional rodents or non-rodents are tested. The undesirable adverse reactions are oft en so subtle, that for optimal assessments excellent knowledge of specific or spontaneous reactions is needed. Th e model must easily be available, costs acceptable and no paucity of historical data representing an obstacle. There will be a continuation of using rats and mice for toxicity evaluations, but for non-rodents a growing refusal is felt in using dogs and monkeys. Th is paper deals with the utility of the minipigs as an animal model in regulatory toxicology. The advantages or disadvantages will be illustrated. Th e Gottingen minipig is a genetically managed model unlike the dog and monkey toxicology models. Th e basis of the small size of the Gottingen minipig does not involve defective genes. Commercial interests in the pig as an agricultural production species have driven the area of pig genomics. There is no equivalent economic driver for progress in the dog or the non-human primate. The Gottingen minipig
is well positioned for the performance of toxicogenomics studies. Th e close sequence homology between pigs and humans suggest that minipigs could be useful for the testing small molecules but also for biotechnology products.
Th e minipig is the only non-rodent model where transgenic animals can be readily generated, and reproductive technologies are well developed in the pig. Th e biology of the minipig is comparable; practically all study types can be performed in the minipig. For reproductive toxicology studies the minipig off ers numerous advantages although the lack of placental transfer of macromolecules may limit the role of the minipig in reproductive testing of biotechnology products. For safety pharmacology studies the minipig is an advantageous model, particularly as regards the cardiovascular system. Th e immune system of the pig is better characterized than that of the dog and as an omnivore the GI-tract reveals similar characteristics. Overall, the mini-pig should be carefully considered as an alternative to dogs and monkeys; but of course, more comparative data is needed for a rigorous assessment of the usefulness and the predictivity of this species for human drug-induced desired and adverse reactions.
