Approximately 30 percent of promising medications have failed in human clinical trials because they are found to be toxic despite promising pre-clinical studies in animal models. About 60 percent of candidate drugs fail due to lack of efficacy.
To address this problem, NCATS, through its Tissue Chip for Drug Screening program, along with other NIH Institutes and Centers, the Defense Advanced Research Projects Agency (DARPA) and the Food and Drug Administration (FDA), leads the development of 3-D platforms engineered to support living human tissues and cells, called tissue chips or organs-on-chips.
Tissue chip devices are designed as accurate models of the structure and function of human organs, such as the lung, liver and heart. Once developed and integrated, researchers can use these models to predict whether a candidate drug, vaccine or biologic agent is safe or toxic in humans in a faster and more effective way than current methods. Learn more about these projects.
The ultimate goal of the program is to accelerate the translation of basic discoveries into the clinic. By creating an integrated human body-on-a-chip, researchers can test the varied potential effects of a substance like a drug across the entire body before any testing in humans.
The NIH Common Fund announced a new collaboration with the FDA to advance regulatory science. In the fall of 2010, NIH and the FDA announced awards as part of the Regulatory Science program. One of those awards included a project to develop a heart-lung tissue chip model to test the safety and efficacy of drugs.
Recognizing the potential to advance tissue chip technology, NIH, the FDA and DARPA held a joint workshop that led to a coordinated effort between the agencies.
NCATS’ launch of the Tissue Chip for Drug Screening program in 2012 resulted in the development of 3-D tissue chips designed to represent a number of human organ systems. NIH awarded 12 projects that supported the development of 3-D cellular microsystems that represent human organ systems and seven projects that explored the use of stem and progenitor cells to differentiate into multiple cell types that represent the cellular architecture within organ systems.
In 2014, researchers began working together on linking individual organs on chips to develop a human multi-organ model system, incorporating several chips that accurately represent various human organs and tissues and captures interactions between different organs. The human model system is being designed to replicate the complex human response to compound exposure and is intended to be used to help predict the safety of potential drugs in a faster, more cost-effective way than current methods. By combining all major organ systems to form a human-body-on-a-chip, NCATS’ ultimate goal is to accelerate the translation of these basic discoveries into the clinic.
NCATS announced a partnership and new funding opportunity with Center for the Advancement of Science in Space (CASIS) in October 2016. The Tissue Chips in Space initiative will enable NCATS and CASIS to collaborate and coordinate efforts that will help refine tissue- and organ-on-chip platforms for in-flight experiments at the International Space Station U.S. National Laboratory (ISS-NL), so that scientists can better understand diseases and translate those findings to affect human health on Earth.
On Oct. 13, 2016, NCATS announced awards for several Tissue Chip Testing Centers that provide a way for independent testing and validation of platforms developed by Tissue Chip for Drug Screening program-supported scientists, ensure the availability of tissue chip technology and promote the adoption of this technology by the broader research community, particularly among regulatory agencies and pharmaceutical companies.
In October 2016, NCATS announced a new funding opportunity through its Tissue Chips for Disease Modeling and Efficacy Testing initiative that will support further development of tissue chip models of human disease that mimic the pathology in major human organs and tissues. The goals of this new initiative are to (1) support studies to develop in vitro disease models using primary tissue or induced pluripotent stem cell (iPSC)-derived patient cell sources on tissue-/organ-on-chips platforms, (2) determine the disease relevance of these models by preliminary testing of key experimental features and (3) test the effectiveness of candidate drugs.
In June 2017, NCATS issued five two-year awards for up to a total of approximately $6 million in response to a funding opportunity to use tissue chip technology for translational research onboard the ISS-NL for the benefit of human health on Earth. During the first phase of the Tissue Chips in Space initiative, researchers will develop and test tissue chips on the ISS-NL in a microgravity environment. In the second phase, they will further demonstrate the functional use of the tissue chip models for more defined experiments on the ISS-NL.
In September 2017, NCATS announced 13 awards to develop 3-D tissue chip research platforms that model disease and test drug efficacy prior to clinical trials. Through the Tissue Chips for Disease Modeling and Efficacy Testing initiative, the Tissue Chip awardees will study a wide range of common and rare diseases, from rheumatoid arthritis, kidney disease and human influenza A viral infection to amyotrophic lateral sclerosis, hereditary hemorrhagic telangiectasia and arrhythmogenic cardiomyopathy. In the second phase of the awards, researchers will partner with pharmaceutical companies to further evaluate the usefulness of validated disease models — those that accurately mimic disease biology — in assessing the effectiveness of candidate drugs.