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Miniaturized organs are joining the fight against COVID-19, cancer

Margaret Lindquist
Senior Director, Industries Content Strategy

In March 2000, the US Food and Drug Administration ordered Rezulin withdrawn from the market. The promising diabetes drug, which had been fast-tracked through the trial process, was linked to at least 61 deaths from liver poisoning.

In 2019, a team led by Dr. Anthony Atala, director of the Wake Forest Institute for Regenerative Medicine (WFIRM), tested an archived version of Rezulin in its lab, and within just two weeks the team was able to see the levels of liver toxicity that had escaped earlier researchers. How? The team used organoids, tiny versions of human organs that are 3D printed and can be used to test drugs both in isolation (to determine the effect on a single organ) and systemically (in organoids that group multiple organs together).

Dr. Atala and team has been generating human tissue for more than a decade, and their “body-on-a-chip” work is starting to be applied to finding vaccines and treatments for COVID-19, cancer, heart disease, and other disorders. Three technological advances in the past couple of years are accelerating the team’s critical work.

One, 3D printing has become much more sophisticated, capable of creating organoids no larger than a pinhead and at volumes exceeding 1,000 per hour. Two, huge volumes of data generated at every stage of the process can now be analyzed for patterns with far greater accuracy thanks to artificial intelligence (AI) and other emerging technologies. Three, cloud services are giving medical researchers ready access to almost unlimited compute and storage capacity to generate more insights from the data that they have, notes Katherine Vandebelt, global vice president for clinical innovation with Oracle, which is contributing its deep cloud and AI expertise to the organoid program, as well as its years of experience working with a variety of health sciences customers.

Building an organoid

To create an organoid, researchers build a scaffold interwoven with microscopic channels that feed nutrients to the organs and remove waste. A 3D printer prints a substance made of human cells mixed with a gelatin “bio-ink” that is printed onto the scaffold “like a layer cake,” Dr. Atala says. Each fabricated organ, some as small as a pinhead, mimics one at full size—hearts beat at about 60 beats per minute and lungs take in air from their surroundings.

The microfluidic system can flood the organoids with drug samples, over and over, the way a human heart constantly recirculates molecules through a body. “You can increase the dose in an organoid to the level you can’t in a human being, so you can see what the toxic effects would be much more quickly,” Oracle’s Vandebelt says. Also, the technology makes it possible to isolate an organ so that “noise” from the other organs doesn’t mask the impact of a drug.

Dr. Atala is creating a consortium that will include pharmaceutical industry representatives, toxicity specialists, animal researchers, regulators, and funding agencies, “So that all this data can be shared and we can all push the field forward together,” he says.

The first partner to join the WFIRM-led consortium was Oracle, with participation from its Oracle Health Sciences team and technologists from its Oracle for Research and Oracle Labs teams, with the goal of developing AI/machine learning capabilities to identify drugs that could be toxic to humans.

“We want to take data from every step of the process, from when you first grow the cells all the way through the production of the organoids, all the way through the laboratory trials and into clinical trials,” says Rebecca Laborde, master principal scientist within Oracle Health Sciences. “If you can have all of that data integrated and then be able to use AI, you’ll see patterns across these large, robust, integrated data sets.”

Bold move for healthcare

The WFIRM program has three main goals:

  1. Save time and money. The first step is to build a library of existing compounds and determine their effect on tissues and organs, then start screening unknown compounds to help create new drugs and therapies. The pharmaceutical industry spends close to $200 billion on drug R&D each year, in many cases screening millions of compounds in the process. But after all that cost and effort, around 90% of the drugs that make it into a Phase I clinical trial never make it out. “If we're able to test these compounds much earlier in the process, you're saving on animal studies, you're saving on resources, you're saving on costs,” Dr. Atala says. “You’re accelerating the development of these drugs much faster for the benefit of the patient.”
     
  2. Improve drug effectiveness. By creating specific disease models—for example, organoids with fibrosis or infection—researchers can study the effect of drugs on the diseases themselves. Currently, Dr. Atala’s team is creating colon and lung organoids and sending them to a biosafety site to be infected with COVID-19. “We take these tissue equivalents to look at infectivity and also to test antidotes so that we can help accelerate the understanding of COVID-19 and screen for new compounds that can be used against the virus,” Dr. Atala says.
     
  3. Embrace personalized medicine. Here, an organoid would be created from a patient’s own cells in order to test potential drugs against the unique DNA and genome of that individual. For example, physicians could create a tumor on a chip and test different cancer drugs before subjecting the patient to the treatment. “There's really no better option than personalized medicine because people process drugs differently,” Dr. Atala says. “They’re different genetically. They’re different epigenetically. They’re different in terms of gender, weight, how they process drugs.”

Dr. Atala and his team's work could reduce the need for animal testing and ultimately replace much of the testing done with human clinical trial subjects. "Being a scientist at a technology company, you're constantly working on cutting-edge things," Oracle's Laborde says. "But this one brings out the next level of dedication in the team. We’re working on something that can really change medicine."

“You're saving on animal studies, you're saving on resources, you're saving on costs. You’re accelerating the development of these drugs much faster for the benefit of the patient.”

Dr. Anthony Atala, Director,
Wake Forest Institute for Regenerative Medicine

 

Learn more about how we’re taking on COVID-19 and read our White Paper on Navigating the Changing Clinical Trial Landscape.

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