How Artificial Dog Intestines Grown by CVM Researchers Could Accelerate Drug Tests, Save Billions

Courtesy of the Des Moines Register
In a tiny cup in a cramped, concrete block office, a billion-dollar idea sits, small enough to fit about 2,000 of itself across the head of a penny.

Iowa State University researchers Jonathan Mochel and Karin Allenspach-Jorn have examined these cups through a microscope for four years, watching stem cells grow into dog small intestines. Their goal? Create a faster way for pharmaceutical companies to determine whether a new drug will work.

Mochel and Allenspach-Jorn's team drops drugs into the tiny organs to measure how much will seep through. In theory, they can show how much of a drug will flow into a patient's bloodstream. If not enough of the substance emerges — or too much of it does — the drugmaker knows the new product doesn't work. 

"It's like poker," Mochel said. "You want to kill the seven and the two and the eight and the three and only keep the jacks and the kings and the queens."

The Iowa Economic Development Authority awarded the company a $25,000 Proof of Commercial Relevance loan in July. 3D Health Solutions then won the 2020 John Pappajohn Iowa Entrepreneurial Venture Competition last month, landing another $40,000. The Iowa Innovation Corp. has also awarded them a $50,000 grant.

Michael Roof, a 3D Health Solutions board member and the chief technology officer for vaccines and immunotherapeutics research at Iowa State, said the company's work appeals to both human and veterinarian drug manufacturers. 

In particular, Allenspach-Jorn said, companies can use the small intestines to test human drugs for Alzheimer's, Crohn's disease and colon cancer. The stomachs of dogs with those ailments are similar to those of humans, possibly because humans have raised and fed dogs in captivity for centuries.

Before testing drugs on rodents, dogs or humans, pharmaceutical companies often try the drugs on cells derived from cancer patients, known as Caco-2 cells. Companies will test how much of the drug seeps through, similar to what the Iowa State team is doing. 

But Mochel and Allenspach-Jorn said the Caco-2 cells are not similar to small intestines, making them a bad way to test a drug's performance.

“It doesn’t actually work at all, and everybody knows it," said Allenspach-Jorn, a professor of translational health and small animal medicine. "You do all of these tests, and you know it’s completely useless. But you still submit it to the FDA so you can show you’ve done it before you go into animals. It’s not useful.” 

Companies spend about $2.6 billion researching a drug before it reaches customers, according to the Journal of Health Economics. Only about 12% of drugs that companies research actually go to market.

Testing a drug's performance on a tiny organ in a lab will allow companies to detect problems before they begin testing on live animals, Roof said. Many times, pharmaceutical companies research a drug on animals for three years before identifying a problem that the 3D Health Solutions team believes it can spot in the lab. 

"They're kind of in a unique space," he said.

Mochel and Allenspach-Jorn are currently conducting a proof of concept study, with $250,000 in funding from the National Science Foundation, to further research their organoids, which are artificially grown masses of cells or tissue that resemble an organ. To show that their small intestines act like that of humans, they are dropping already developed drugs into the organoids and monitoring how much of the drug seeps through.

Researchers record the amount that emerges and compare the figures to what the U.S. Food and Drug Administration already knows about those compounds. 

If the results are promising, Mochel and Allenspach-Jorn will apply for a second National Science Foundation grant in March, this one for $1 million. They will test the small intestines against more drugs.

Mochel said there is a "50-50" chance that the National Science Foundation will approve their application for the second phase. He said the organization ranked their previous grant proposal first among 730 applications it received across the country. 

Still, he believes the research will take years — if not decades — before big pharmaceutical companies begin using the small intestines to test their new drugs.

"We're not making any money and probably won't for a while," Allenspach-Jorn said. "But if we can get to the point where someone can acquire the business and make it into something bigger, I think it will be real nice."

The process begins at the Hixson-Lied Small Animal Hospital on Iowa State's campus, where Allenspach-Jorn collects stem cells from some dog patients, with their owners' permission.

Researchers grow the stem cells in tiny cultures that look like clear, plastic, thumb-sized cups. As they grow into an organ, the stem cells birth other "daughter" cells. The researchers drop in "growth factors," proteins that instruct the cells to become larger and develop functions — producing mucus and hormones and absorbing whatever enters the small intestine.

Researchers can now see the insides of the organ. They are looking at the part of a body where a drug rests after a patient swallows it, the medication freed from the capsules that dissolved in stomach acid on the way down.

The researchers drop a test drug and solution into the test organ. Then, they wait. A receptor cup, seated under the sticky surface that holds the small intestine, will catch the drugs as they seep through. This tells researchers how the small intestine performed. 

Then, they experiment again. About 100 times so far this year.

"We can save dogs from going through this," Allenspach-Jorn said. "And save the biopharmaceutical industry a lot of money."