FIGHTING FOR AIR

A sinister intruder, the coronavirus known as SARS-CoV-2 infects the body in the same way other viruses do—by hijacking healthy cells and forcing them to create copies of the virus. But this virus has a secret weapon: spiky surface proteins that easily bind to cells in the lungs, making the lungs especially susceptible to infection.

As the lungs fight the virus, the body’s immune system triggers inflammation to help defend against the intruder. While lung inflammation can cause breathing difficulties, most people recover from COVID-19. But in the most serious cases, the body’s immune system may go into overdrive, causing widespread inflammation that can damage lung tissue.

This can lead to acute respiratory distress syndrome (ARDS), a life-threatening injury that allows fluid to leak into the lungs, causing extreme breathing difficulties. With no cure for ARDS, physicians can only offer patients  supportive care, often using a ventilator to assist breathing in hopes that the lungs  will eventually heal.

Breathing in hope
Physician-scientist Holger Eltzschig, MD, PhD, has studied ARDS for nearly two decades. In a 2013 preclinical study, his team found that a specific protein can help protect the lungs by reducing inflammation and fluid buildup during ARDS. Now, in partnership with clinical expert Bentley J. Bobrow, MD, the team is on the precipice of unlocking an innovative treatment that activates this protein to treat ARDS in patients with COVID-19.

With Bobrow serving as principal investigator, the team is leading a randomized clinical trial to determine whether an investigational oral drug called vadadustat—which activates the protective protein—can help COVID-19 patients with ARDS. Although vadadustat, created by Akebia Therapeutics, is currently in development to treat patients with anemia of chronic kidney disease, Eltzschig quickly recognized its potential to defend against one complication of COVID-19.

“All of my lab’s research in ARDS over the last 20 years has led to this moment,” says Eltzschig.  “Dr. Bobrow and his team’s expertise in leading clinical trials allows us to translate this research into a therapy for patients who need it most.”

With help from the UTHealth COVID-19 research task force, the team organized the clinical trial in three short months—a feat that ordinarily takes longer than a year. The team will enroll up to 400 patients with COVID-19 who require supplemental oxygen in the randomized trial, with patients receiving either vadadustat or a placebo. In August 2020, the team enrolled the first patient.

“Every day in the Department of Emergency Medicine, we see patients who are critically ill with COVID-19—oftentimes they are only hanging on with help from a ventilator,” says Bobrow. “That motivates our team to work at warp speed to develop better treatments.”

The trial, initially funded by UTHealth Center for Clinical and Translational Sciences and Akebia Therapeutics, began at Memorial Hermann Health System and will be expanded to other sites across the United States if the team sees promising results. In September 2020, the team received a $5.1 million grant from the United States Department of Defense, recognizing the trial’s potential to help protect military personnel from ARDS. 

“ARDS is proving to be one of the greatest challenges of the COVID-19 pandemic, but we have the people and ideas to overcome it,” says Bobrow. “This trial is a product of the incredible research and collaborations happening at UTHealth, and a prime example of why we are positioned to tackle a wide variety of health challenges.”

The next generation of researchers
Although ARDS can be a serious consequence of the virus, Nathan Berg, a student in the MD/PhD program at McGovern Medical School at UTHealth and The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, remains hopeful that his research in acute lung disease will make a difference.

“At the onset of the pandemic, I knew our work in acute lung injury would have the opportunity to help find a solution to ARDS,” says Nathan. “This is what we study every day, and now we have a chance to apply our research to help people with COVID-19.”

Under his mentors, Eltzschig and Xiaoyi Yuan, PhD, Nathan has dedicated his entire graduate education to studying acute lung injury, a result of ARDS.

“My main research interests include harnessing the protective properties of lung cells to defend against lung injury and finding ways to subdue the overactive immune system response to lung injury,” Nathan says. “Breakthroughs in these areas could lead to better therapies for people who suffer from deadly lung injuries, such as ARDS caused by COVID-19"

“Being part of the MD/PhD program during the pandemic has shown me the importance of being able to translate research from the lab to the bedside to help patients who need it most,” he says. “Pathogens like COVID-19 are among the biggest threats to health. As I grow in my career as a physician-scientist, I want to continue searching for ways to help us overcome them.”