In a lab at Johns Hopkins University School of Medicine in Baltimore, a blob of human tissue designed to mimic the properties of an intestine swells with fluid as scientists try to bring on symptoms associated with a bout of diarrhea.
It’s the first step to determine whether the structure, known as an organoid, can be used to test treatments for this ailment, which the World Health Organization says kills about 1.5 million children a year. The work is one of several similar efforts nationwide that are part of a push to make early product testing cheaper, faster and less prone to failure for Pfizer Inc., Merck & Co. and other drugmakers. The technology may one day help them spot drug reactions within days, or even hours, said Mark Donowitz, the Johns Hopkins research leader.
“That would speed the delivery of new medicines to patients that need them,” Kathy Hudson, acting deputy director of the National Institutes of Health unit funding the research, said in a telephone interview.
The Johns Hopkins scientists are set to report their findings at a meeting of the American Gastroenterological Association next week in Chicago, Donowitz said in an interview at his lab. While that research is among the most advanced being done in the U.S., more is coming.
Hudson’s Bethesda, Maryland-based unit, the National Center for Advancing Translational Sciences, last month said it was handing out $13 million in grants to 17 research organizations. The NIH, part of the U.S. Department of Health, is the world’s biggest source of funding for medical research, according to the agency’s website.
The money is part of a five-year, $70 million NIH effort to expand drug-testing methodology using organoids and a similar technology that fuses human cells, designed to function like organs, onto clear silicon chips. The chips, about the size of a quarter, would be easy to collect and work with.
In addition to moving the drug development process along more quickly, the new technology may be more accurate, according to Hudson. About 30 percent of drug compounds that had promising results in tests on animals fail in human trials because of potential safety risks, she said.
“If companies are better able to get signals of toxicity early and abandon toxic compounds early, that then saves them money,” Hudson said.
Pfizer, based in New York, spent $9.11 billion on research and development last year. Whitehouse Station, New Jersey-based Merck’s R&D expenses were $8.4 billion.
Some pharmaceutical companies have already begun exploring the use of human tissue grown in the laboratory for testing purposes.
In 2010, for instance, researchers at Basel, Switzerland-based Roche Holding AG used stem cells to confirm toxicity from an antiviral medication the company had been developing. Roche had already abandoned the drug two years earlier after tests in rodents and rabbits showed it caused side effects in the heart. Had stem cell-derived heart tissue been available then, the company could have pulled the plug early, saving two years of work and millions of dollars.
The NIH isn’t the only U.S. agency pushing the new technology. The Defense Advanced Research Projects Agency, the military’s research arm, has given Harvard University’s Wyss Institute in Boston $37 million to develop a way to integrate 10 organs-on-a-chip to mirror the complexity of the human body, the institute said in a July 24 announcement.
The Harvard program is led by Donald Ingber, the institute’s founding director. It is developing coin-sized chips with channels carved into them that are filled with human cells, as well as tiny pumps and other mechanical elements, to replicate how organs work at the cellular level.
For instance, the chips attempting to replicate the body’s ability to breathe carry both lung and capillary cells, separated by a porous membrane that has air on one side and blood on the other.
Drugmakers, especially those open to “scientific risk-taking and pushing the envelope a little bit, will be standing in line waiting to try these things,” said Bob Chapin, a senior research fellow for Pfizer who tests for toxicity in the earliest stages of drug studies.
“I’ll be one of the people clamoring to try a beta version,” said Chapin, who said he was speaking for himself, and not on behalf of his company.
The organoid at Johns Hopkins was derived from human stem cells. When scientists elevated levels of metabolic regulators in the tiny intestine that affect sodium absorption and chloride secretion, water accumulated in its cavity and it expanded. This is essentially what happens when a person has diarrhea, proving the organoid is functional, the researchers said.
“This kind of preliminary data is convincing and lets the NIH know we’re not wasting the American dollar,” said Donowitz, the lead researcher.
The eventual goal is to use the organoid to test potential treatments for diarrhea. In the U.S., one-third of acute cases are food-borne illnesses and the remainder related to viruses or bacteria, Donowitz said. There are about 2 billion cases of diarrhea a year globally, and the disease is the second-biggest killer of children under five, the WHO says.
The biggest benefit of the work may be the small amount of compound needed to conduct a trial versus rodent studies, Pfizer’s Chapin said. Early studies require 50 to 100 rats per molecule and potentially hundreds of grams of compound for testing, he said.
In contrast, researchers might need about 3 milligrams of a compound to test on a cell culture.
While it will probably be a while before the first organoids and cell chips are used to test pipeline products, Chapin said he’s looking forward to the opportunity.
“The sooner the better,” he said.