April 17, 2014: 3-D Disease Models May Better Predict Therapeutic Success

In order for a new drug to be approved by the FDA for use in patients, it must be shown to be effective in clinical trials. Currently, more than 80 percent of new drugs tested in clinical trials fail, preventing therapies from reaching the medicine cabinet and causing enormous loss of time and expense. To address this translational roadblock, NCATS is developing new technologies to better predict which drugs will be safe and effective in clinical trials.

Once a molecule or compound has been shown to have an effect that is relevant to a disease, researchers try to predict if it will work in people by testing it in isolated cells and animal models that mimic some of the characteristics of the human disease. Unfortunately, current cell and animal models often are poor predictors of how people will react to a drug. This probably is because in the body, cells are never isolated, and animals frequently respond differently to drugs than people do.

Remarkable advances in tissue engineering, stem cells and biosensor technologies now make it possible to combine the best of cellular and animal models to create better testing systems for new drugs. These models use human cells, usually taken from patients with the disease under study, that are placed in 3-D clumps made of multiple cell types in a cellular environment that more closely resembles the complex and interactive systems in the human body.

NCATS is fostering the development of these technologies via collaborations with academia, industry and small businesses. For example, the Tissue Chip for Drug Screening initiative is an interagency collaboration among NIH, the Defense Advanced Research Projects Agency and the Food and Drug Administration to develop 3-D human tissue chips that model the structure and function of human organs, such as the lung, liver and heart. Once they are developed, researchers can use these models to predict whether a candidate drug, vaccine or biologic agent is safe and effective in humans.

Earlier this year, NCATS partnered with the bioprinting company Organovo and the National Eye Institute (NEI) to develop a more clinically predictive tissue model for eye diseases. NCATS now houses Organovo’s NovoGene MMX Bioprinter, where researchers from NCATS and NEI are creating 3-D, architecturally accurate eye tissue to test the safety and effectiveness of candidate drugs. NCATS researchers are also working with Organovo to develop 3-D skin and other tissue models.

Another new NCATS partnership — with biotechnology company InSphero — is allowing NCATS scientists to develop and test the effects of potential anti-cancer drugs in 3-D, pancreatic and ovarian tumor models. Both the InSphero and Organovo platforms will enable researchers to test more candidate drugs in much less time than would be possible in animal models, producing results that promise to be more predictive of therapeutic success in human patients.

Our focus on 3-D disease models exemplifies the NCATS approach: developing, demonstrating and disseminating transformational technologies to overcome critical translational roadblocks via team-science based collaboration, ultimately catalyzing the delivery of more therapies to more people more quickly.

Christopher P. Austin, M.D.
National Center for Advancing Translational Sciences