Amanda Rennig

Graduate student Amanda Rennig will present 

"Using Organs-on-Chips to Study Metabolism and Toxicity"

on December 5, 2017 at 4:10 PM in Neville Hall, Room 3.

 

Abstract:

Demonstrating safety of drug candidates is a critical step of the drug development process. Lack of safety or the potential for toxicity is also one of the main reasons drug candidates fail to be approved by the Food and Drug Administration (FDA). In most cases, drug candidates fail once they get to human trials due to toxicity that was not detected previously during pre-clinical trials.1 The tests used to predict toxicity during pre-clinical trials, such as animal models and cells in culture, are not always reliable models for predicting toxicity in humans because of the differences in biochemistry occurring in test animals compared to humans.2 Differences in ADME (absorption, distribution, metabolism, and excretion) of the drug in the animal model can make the drug more or less toxic to that animal than it would be to a human. Additionally, using cells in culture can lead to misleading toxicity results due to the cells being isolated and not interacting with the other surrounding body tissues and systems.

The National Institutes of Health (NIH), FDA, academia, and private industry have invested extensive resources to develop organs-on-chips that can mimic the biological functions of the human body.1,3 By mimicking the functions of the human body, the organs-on-chips could prove to be more successful for use in pre-clinical safety studies than animal models or cell cultures. Some of the current research studies focus on the development of functioning organs-on-chips and utilizing them to study metabolism and toxicity. For example, an organ-on-chip model of the human brain has been developed to study how inflammatory stimulation of the blood-brain barrier changes its ability to act as a protective barrier and the associated metabolic consequences.4 Also, linking kidney and liver organs-on-chips to create a more complex model enabled a research group to study the metabolism and toxicity of two model drugs that are used in cancer treatment and treatment of cardiovascular disease.2

References:

National Institutes of Health: News Releases. https://www.nih.gov/news-events/news-releases/nih-awards-15-million-supp... (accessed October 27, 2017). Li, Z.; Jiang, L.; Zhu, Y.; Su,W.; Xu, C.; Tao, T.; Shi, Y.; Qin, J. Toxicology in Vitro [Online Early Access]. DOI: 10.1016/j.tiv.2017.10.005. Published Online: October 3, 2017. http://www.elsevier.com (accessed Nov 9, 2017). Fitzpatrick, S. U.S. Food and Drug Administration: FDA Voice. https://blogs.fda.gov/fdavoice/index.php/2017/04/organs-on-chips-technol... (accessed October 27, 2017). Brown, J. A. et al. Journal of Neuroinflammation 2016, 13, 306-323.