REPROCELL can directly compare drug responses across species, helping you to translate your data from preclinical animal species to humans.
It is generally recognised that there is an over-reliance on animal models in the prediction of clinical effects, in particular with respect to the demonstration of efficacy in humans and the translation from preclinical species. REPROCELL’s ability to perform comparative in vitro studies, including human tissue, highlights potential species differences early in the drug development process. This has become especially important in translational medicine, through preclinical safety studies and the need improve the prediction of efficacy by using phenotypically-relevant fresh diseased human tissue.
For example, the 5-hydroxytryptamine (5-HT, serotonin) pathway is more prominent in the coronary artery function of human than in canine tissues, a standard preclinical safety species and pig, a favoured cardiac model species. The above graph shows the marked differences in responses of isolated arteries to 5-HT between humans and dogs.
A further example below shows clear differences in the potency of a PDE type 2 inhibitor in humans and dogs, such that assessment of test compound effects in dogs would under-estimate the effect in humans.
It is not only in the vascular system that such differences exist between species.
A review of the literature illustrates that the potencies of various bronchoconstrictors differ markedly between the main preclinical species (see comparison below), with no species mimicking the human situation. Approximately one-third of all respiratory abnormalities during human clinical trials can be attributed to unforeseen drug-mediated changes in airway resistance. Taken together, these findings suggest that the prediction of human bronchoconstriction (and therefore airway resistance) could be vastly improved by greater use of human fresh bronchial tissues or by an early cross-species comparison between preclinical species to explore the relevance of the animal model to humans.
Although animal models continue to be a mainstay in the testing of potential new drug therapies, early cross-species comparisons with fresh functional human tissues increases confidence that the results will translate to patients. Moreover, such assays play an important role in the “3Rs”, the refinement, reduction and replacement of tests in animals.
REPROCELL has been providing contract research services to the pharmaceutical industry since 2002 and has established itself as the world leader in the use of fresh isolated tissues to better predict drug activity prior to clinical trials. The clear commercial benefits of reducing risk by generating early human data on safety, efficacy and absorption are making human tissue research a routine part of drug development. REPROCELL’s expertise in all areas of human tissues research including sourcing, handling and experimenting on human tissue allows us to act as your “Human Tissue Research Department”.
Contact us for further information on our range of tests in fresh functional human tissues.