HUMAN LIVER MODELS FOR FASTER, SAFER DRUG DEVELOPMENT



Sangeeta N. Bhatia
Health Sciences and Technology
Electrical Engineering and Computer Science

Each new pharmaceutical drug costs roughly $1 billion to develop, and late-stage failures, such as Vioxx and Rezulin, are dangerous and enormously expensive. As many as 60 percent of drug failures are due to poor absorption, distribution, metabolism, excretion and toxicity (ADME/Tox) profiles that might have been predicted if models of human liver tissue were available earlier in drug development. This project is developing miniature human liver tissue in an industry-standard, multiwell plate format that can be used for more effective ADME/Tox studies earlier in the drug development process.

The liver is the major site of drug metabolism and toxicity. However, the function of human liver cells deteriorates rapidly in the laboratory, thereby limiting their utility for drug development. The liver tissue under development here stabilizes and enhances the function of liver cells, greatly extending their life in the laboratory. It could save drug developers a significant portion of the $3 billion spent each year on ADME/Tox studies, helping them direct resources toward truly promising compounds rather than those doomed to fail.

A prototype device has been developed and has shown promise in pilot studies of drug metabolism and toxicity. This project will explore storage and shipping conditions to deliver the in vitro hepatocytes to customers and further proceed towards commercialization.