Nav: Home

Enhancing drug testing with human body-on-chip systems

January 27, 2020

The U.S. Food and Drug Administration (FDA) approves only 13.8% of all tested drugs, and these numbers are even lower in "orphan" diseases that affect relatively few people.

Part of the problem lies in the imperfect nature of preclinical drug testing that aims to exclude toxic effects and predetermine concentrations and administration routes before drug candidates can be tested in people. How new drugs move within the human body and are affected by it, and how drugs affect the body itself, cannot be predicted accurately enough in animal and standard in vitro studies.

"To solve this massive preclinical bottleneck problem, we need to become much more effective at setting the stage for drugs that are truly promising and rule out others that for various reasons are likely to fail in people," explains Prof. Donald Ingber, M.D., Ph.D., founding director of Harvard University's Wyss Institute for Biologically Inspired Engineering, co-author of two new studies on the subject published in Nature Biomedical Engineering on January 27, 2020.

Co-led by Dr. Ben Maoz of Tel Aviv University's Department of Biomedical Engineering and Sagol School of Neuroscience and over 50 colleagues, a team of scientists at TAU and Harvard have now devised a functioning comprehensive multi-Organ-on-a-Chip (Organ Chip) platform that enables effective in-vitro-to-in-vivo translation (IVIVT) of human drug pharmacology.

"We hope that this platform will enable us to bridge the gap on current limitations in drug development by providing a practical, reliable, relevant system for testing drugs for human use," says Dr. Maoz, co-first author of both studies and former Technology Development Fellow at the Wyss Institute on the teams of Prof. Ingber and Prof. Kevin Kit Parker, Ph.D., the latter of whom is also a leading author of both studies.

In the first of two studies, the scientists developed the "Interrogator," a robotic liquid transfer device to link individual "Organ Chips" in a way that mimics the flow of blood between organs in the human body.

Organ Chips are microfluidic devices composed of a clear flexible polymer the size of a computer memory stick that contains two parallel running hollow channels separated by a porous membrane and independently perfused with cell type-specific media. While one of the channels, the parenchymal channel, is lined with cells from a specific human organ or functional organ structure, the other one is lined with vascular endothelial cells presenting a blood vessel. The membrane allows the two compartments to communicate with each other and to exchange molecules like cytokines and growth factors, as well as drugs and drug products generated by organ-specific metabolic activities.

The team then applied their Interrogator automated linking platform and a new computational model they developed to three linked organs to test two drugs: nicotine and cisplatin.

"The modularity of our approach and availability of multiple validated Organ Chips for a variety of tissues for other human Body-on-Chip approaches now allows us to develop strategies to make realistic predictions about the pharmacology of drugs much more broadly," says Prof. Ingber. "Its future use could greatly increase the success rates of Phase I clinical trials."

The researchers accurately modeled the oral uptake of nicotine and intravenous uptake of cisplatin, a common chemotherapy medication, and their first passage through relevant organs with highly quantitative predictions of human pharmacokinetic and pharmacodynamic parameters.

"The resulting calculated maximum nicotine concentrations, the time needed for nicotine to reach the different tissue compartments, and the clearance rates in the Liver Chips in our in vitro-based in silico model mirrored closely what had been measured in patients," concludes Dr. Maoz.

The multidisciplinary research project is the culmination of a Defense Advanced Research Projects Agency (DARPA) project at the Wyss Institute. Several authors on both studies, including Prof. Ingber, are employees and hold equity in Emulate, Inc., a company that was spun out of the Wyss Institute to commercially develop Organ Chip technology.
-end-
American Friends of Tel Aviv University supports Israel's most influential, comprehensive and sought-after center of higher learning, Tel Aviv University (TAU). TAU is recognized and celebrated internationally for creating an innovative, entrepreneurial culture on campus that generates inventions, startups and economic development in Israel. TAU is ranked ninth in the world, and first in Israel, for producing start-up founders of billion-dollar companies, an achievement that surpassed several Ivy League universities. To date, 2,500 US patents have been filed by Tel Aviv University researchers -- ranking TAU #1 in Israel, #10 outside of the US and #66 in the world.

American Friends of Tel Aviv University

Related Nicotine Articles:

Nicotine vapour more rewarding for adolescents than adults
University of Guelph researchers are the first to discover that adolescents react differently to e-cigarette vapour than adults.
Understanding the link between nicotine use and misuse of 'benzos'
Lately, misuse of prescription benzodiazepines (such as alprazolam or Xanax, and diazepam or Valium) has been linked to nicotine use.
Popular electronic cigarette may deliver nicotine more effectively than others
When it comes to nicotine delivery, not all electronic cigarettes are created equally, according to Penn State researchers.
Fetal nicotine exposure harms breathing in infants
Exposure to nicotine during development inhibits the function of neurons controlling the tongue, according to research in newborn rats recently published in eNeuro.
Diabetes drug relieves nicotine withdrawal
A drug commonly used to treat Type II diabetes abolishes the characteristic signs of nicotine withdrawal in rats and mice, according to new research published in JNeurosci.
The nicotine in e-cigarettes appears to impair mucus clearance
E-cigarette vaping with nicotine appears to hamper mucus clearance from the airways, according to new research published online in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.
Truth telling about tobacco and nicotine
In 'Truth Telling about Tobacco and Nicotine,' PRC researchers explain that, although there is agreement among researchers about evidence that vaping can be less harmful than combustible cigarettes, the tobacco control community remains divided about how to communicate -- or even whether to communicate -- information about the relative risks of tobacco and nicotine products.
This is a neuron on nicotine
Newly developed sensors visually illustrate how nicotine affects cells from the inside out.
New data suggests nicotine while pregnant alters genes
A University of Houston biomedical research team is reporting that a possible cure for addiction may be found by following the pathways of significantly altered dopamine neurons in newborns who were chronically exposed to nicotine in utero.
Ex-smokers might be better off with high rather than low nicotine e-cigs
Vapers using low rather than high nicotine e-cigarettes may be using their devices more intensely, potentially increasing the risk of exposure to toxins in the vapour, according to new research funded by Cancer Research UK and published in Addiction today.
More Nicotine News and Nicotine Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Listen Again: The Power Of Spaces
How do spaces shape the human experience? In what ways do our rooms, homes, and buildings give us meaning and purpose? This hour, TED speakers explore the power of the spaces we make and inhabit. Guests include architect Michael Murphy, musician David Byrne, artist Es Devlin, and architect Siamak Hariri.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.