Pulmonary Medicine Scientists Adapt Research to COVID-19
Research teams in the Division of Pulmonary Medicine have started pursuing answers to understanding and treating coronavirus. Below are a few of the highlights.
Exploring Blood Biomarkers to Predict Response and Impact of Gene Therapy
A team of scientists led by Assem Ziady, PhD, co-director of the Imaging and Biomarker RDP Core, are adapting successful lung disease research to the challenges of treating COVID-19.
Their two primary COVID-related projects are exploring blood biomarkers to predict decline, and using gene therapy to induce immune response.
Ziady has teamed with colleagues Kristin Hudock, MD, and Rhonda Szczesniak, PhD, to adapt approaches used to identify biomarkers of lung function decline in cystic fibrosis. Their goal is to explore biomarkers that might predict the course of COVID infection.
“With COVID, some patients are barely symptomatic while others have a very severe response to the disease. If we had biomarkers that predicted responses, patients identified as infected could be screened early and put in a category of high or low risk,” says Ziady. “If we had a biomarker that identified them as high risk, they might not be sent home - they could remain in the hospital or be monitored more closely.”
Ziady’s team is also investigating a reapplication of gene therapy approaches developed to correct the genetic defect in cystic fibrosis, to create immunity against SARS CoV-2.
“We are exploring whether expressing small portions of the virus might actually confer immunity in the host,” Ziady explains. “If I give you an attenuated virus, or the virus itself, it can make you sick, but if I give you a piece of the virus, then your body can mount an immune response against that, and the hope is that response will neutralize the intact virus and make you immune to infection, at least temporarily, if not long-term.”
Study Investigates Cystic Fibrosis Gene’s Impact on COVID-19 Infection
The gene responsible for cystic fibrosis can play a role in COVID-19 infection, says Anjaparavanda Naren, PhD, Director of the Cystic Fibrosis Research Center. Naren’s study of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene in cystic fibrosis led him to hypothesize about its role in COVID-19.
“The CFTR protein, which causes cystic fibrosis if lacking, causes diarrhea when hyperactive,” Naren says. “With COVID-19, up to 35% of patients don’t show respiratory symptoms, they show GI symptoms, such as abdominal pain and diarrhea. We are proposing that this happens because CFTR interactions are affected under COVID conditions.”
Naren’s theory is that the COVID-19 spike protein gains entry to the intestinal epithelial cells by binding to the angiotensin-converting enzyme (ACE2) receptor on the cells. This revs up CFTR activity, causing increased fluid secretion and diarrhea. His team will explore how this binding of COVID-19 spike proteins happens in the gut, and how it might be thwarted.
In a collaboration with Anil Jegga, DVM, Naren and his team will test the repurposing of as many as 15 FDA-approved small molecule compounds to see if they can effectively stop the virus from binding to the epithelial cells of the intestinal tract.
They have applied to the National Institutes of Diabetes, Digestive and Kidney Diseases (NIDDK), which funds their CFTR research, for a supplemental grant to prove their theory - and to test the compounds to treat it.
“We already see a difference in the binding of the COVID-19 spike protein. So we have proof of concept that this concept works. Now we have to purify significant amounts of proteins. That is why we are asking for funding. We are developing our own spike proteins to test this further.”
