Primary Cell-Based Assays Reflect Disease Physiology
Since it is known that various cell types are present in diseased tissue, BioSeek (www.bioseekinc. com) developed in vitro systems that expose cells to a disease environment. "Tissue models are generally healthy tissue, but when you have disease, there are multiple cells that infiltrate the disease site," says Ivan Plavec, Ph.D., senior director of technology development. "So if you want to study a drug effect, or use your system to study or develop drugs, you need to create a disease-like environment," explains Dr. Plavec.
BioMAP systems are cell-based assays that use human primary cells, or combinations of primary cells, in a single well to capture cell-cell interactions. These are simultaneously activated to replicate pathway interactions found in disease physiology.
"We'll combine cells to come up with something that's most relevant for that particular tissue. Then we take the panel with several BioMAP systems, profile compounds in the panel, and use this as a tool to develop therapeutics," states Dr. Plavec.
The in vitro environments are optimized such that the cell response represents what is occurring in vivo. Then test compounds are added to the cell cultures. "We want to see that the response to drug treatment is in agreement with what's known about the effect of that drug in vivo. Once we see these two being in close approximation, then we say we're modeling the right biology," says Dr. Plavec.
Optimized sets of protein readouts that represent the biology of disease areas are measured. Depending on the mechanism of action, compounds induce specific changes in the expression of protein readouts, providing a specific BioMAP profile. These profiles are stored in the company's database and analyzed using proprietary statistical and modeling algorithms. Newly identified leads are compared to the BioMAP profile of known therapeutics to identify compounds that exhibit desired activity.
Current tissue models include skin, vasculature, lung, and joint. Dr. Plavec says although the company initially started with inflammation, they are interested in expanding into cardiovascular disease, metabolism, heart disease, and fibrosis. In addition, with companies more interested in biology, Dr. Plavec says their in vitro disease models should be better predictors of drug activity than animal models.