Researchers will use “mini lungs in a dish” to test promising drug candidates
Sanford Burnham Prebys Medical Discovery Institute has received an award from the California Institute for Regenerative Medicine (CIRM) to advance promising drug candidates for COVID-19. The award is part of CIRM’s Quest Awards Program, which promotes promising new technologies that can be translated to enable broad use and improve patient care. Evan Snyder, M.D., Ph.D., a professor and director of the Center for Stem Cells and Regenerative Medicine at Sanford Burnham Prebys, is the principal investigator of the grant; and Sandra Leibel, M.D., an assistant professor at UC San Diego, who is currently conducting research in the Snyder lab, is the co-principal investigator.
“We are honored to receive this important award from CIRM,” says Snyder. “As the world continues to grapple with this rapidly spreading disease, our scientists will continue to work around the clock to find solutions for this public-health emergency. This grant will allow us to test drugs for effectiveness against SARS-CoV-2, and tackle key research issues that need to be addressed for this pandemic as well pandemics we may encounter in the future.”
With the support of the CIRM award, the research team will test two existing drugs, ONO5344 and VBY825, against “mini lungs in a dish” that have been infected with SARS-CoV-2. The drugs were brought to the team’s attention by Sumit Chanda, Ph.D., director of the Immunity and Pathogenesis Program at Sanford Burnham Prebys; and Laura Riva, Ph.D., a postdoctoral researcher in Chanda’s lab, who performed a high-throughput screening study of the reFRAME drug repurposing collection—a library of more than 12,000 existing drugs that have been FDA approved or have extensive human safety and toxicity profiles. The selected drugs are protease inhibitors that emerged as the most promising candidates to hit the “Achilles heel” of SARS-CoV-2.
“To move these drugs forward, we need to test them in a clinically relevant system,” says Leibel. “Mini lungs are an ideal system to further investigate these drugs because they can emulate the actual COVID-19 disease, and they may help us bypass animal testing and fast-track them to patients.”
The “mini lungs in a dish,” also referred to as “lung organoids,” are created by taking a sample of skin cells and “coaching” them in the lab to become human induced pluripotent cells (hiPSCs). With a little more “coaching,” hiPSCs can be transformed into 3D structures that have all of the cell types and structures that lungs have: airway cells, cells that make key proteins, and even cells with cilia. These 3D structures can be invested with inflammation cells and blood vessel cells to make a complete mini lung.
“Mini lungs will also help us answer why some people with COVID-19 fare worse than others,” says Snyder. “Because they are made from hiPSCs, which come from patients and retain most of the characteristics of those patients, we can make ‘patient-specific’ mini lungs. We can compare the drug responses of mini lungs created from Caucasian, African American, and Latino men and women, as well as patients with a reduced capacity to fight infection to make sure that therapies work effectively in all patients. If not, we can adjust the dose or drug regime to help make the treatment more effective.
“We can also use the mini lungs experimentally to evaluate the effects of environmental toxins that come from cigarette smoking or vaping to make sure the drugs are still effective; and emulate the microenvironmental conditions in the lungs of patients with co-morbidities such as diabetes, and heart or kidney disease.
“Until a vaccine becomes readily available, a drug that suppresses the severity and contagion of COVID-19 might be the next best thing,” adds Snyder.