Preclinical drug discovery is essentially concerned with disease models that mimic the human condition. These models can use animals, cells or purified protein. In vivo animal models are used for target validation and proof of efficacy prior to introduction into man during clinical trials. In vitro models used for small molecule screening purposes put the emphasis on the target: either as a binding assay using purified protein or as cell-based functional assay with the receptor target over-expressed in an immortalized cell line allowing unlimited amounts to be produced of concise response.
While in-vitro models provide statistically consistent information and workflows that are highly automatable to allow screening vast libraries and in-vivo models in mammals may provide efficacy evidence necessary for IND submission to the FDA, there is growing concern that the information is of questionable biological relevance in man. This is made evident by the marked decline in NCEs brought to the market over the last decade.
Most Pharma and large Biotech are now channeling resources into the investigation and use of human primary cells in preclinical drug discovery. It is thought that this model most closely resembles what occurs in clinical trials. Key issues are supply and assay reproducibility due to the limitations in cell propagation and source variability. Hepatocytes and peripheral blood mononuclear cells (PBMCs) are most used in preclinical drug discovery at the moment, but the range of cell types is ever increasing. The promise of stem cells alleviating supply and reproducibility issues has not yet been realized, but is an area of highly active research.
BioTek Instruments is working in this area developing assays with hepatocytes and human umbilical vein endothelial cells (HUVECs). Stay tuned for exciting results …
By: BioTek Instruments