Tiny organ-like structures grown in the laboratory to behave like human lungs and colons can be used to rapidly screen drugs and identify those with potential as COVID-19 treatments, researchers reported on Wednesday in Nature.
Compared with traditional pre-clinical approaches, in which drugs are tested in cells from monkeys or from human cancer patients, these so-called organoids more faithfully mimic the complex cell types and structure of human tissues, according to Dr. Shuibing Chen and Dr. Robert Schwartz of Weill Cornell Medicine in New York.
Their team developed organoids containing types of lung and colon cells that are known to become infected in people with COVID-19.
“This study demonstrates that you can use organoids derived from human pluripotent stem cells as a platform to discover drugs that block SARS-CoV-2 infection or progression of COVID-19,” said co-senior author Dr. Todd Evans, the Peter I. Pressman M.D. Professor of Surgery and associate dean for research at Weill Cornell Medicine. “Also, this platform can screen drugs that are already FDA-approved, which provides the added advantage of possibly being able to repurpose drugs that we already know are safe in patients, and therefore have the potential to move quickly into clinical trials.”
In collaboration with teams at Columbia University and Icahn School of Medicine at Mount Sinai, they screened 1,200 FDA-approved drugs and found three that showed activity against the novel coronavirus, including the cancer drug imatinib, sold as Gleevec by Novartis.
“We also showed that we can transplant these human organoids into a mouse, giving us a model to evaluate the efficacy of different compounds in human cells in a whole animal context,” Dr. Chen said. She adds that, to her knowledge, this is the first time organoids have been used as part of a high-throughput screening platform for any purpose on a broad scale.
It is currently being tested in four different COVID-19 clinical trials.
Dr. Schwartz added that because organoids can be made for every human organ type, this screening method could help to identify drugs that treat numerous harmful effects of COVID-19 disease. “If in fact we find the same drugs keep coming up, that’s a hopeful sign that they could be effective for treating systemic infections,” he said.
