Experimental Stem Cell Therapy a Potential Weapon in COVID-19 Fight
Ottawa-based researchers pivot at lightning speed to launch study on treating related respiratory failure
As the grim COVID-19 statistics continue to rise – globally, more than four million confirmed cases and nearly 300,000 deaths were reported as of early May 2020 – researchers around the world are springing into action to identify potential treatments and vaccine candidates.
Now, a team based at The Ottawa Hospital is redeploying lessons learned from the world’s first safety trial assessing the use of mesenchymal stem/stromal cells (MSCs) for treating runaway inflammation in patients with severe sepsis to treat the intense lung inflammation that causes Acute Respiratory Distress Syndrome (ARDS) in COVID-19 patients.
ARDS is a type of serious respiratory failure involving extensive inflammation and fluid buildup in the lungs arising from a severe immune response to infection. The inflammation prevents proper oxygenation of the bloodstream, impacting all of the body’s organs. ARDS is also commonly seen in patients with sepsis, and research suggests that it develops in as many as 40% of patients who develop COVID-19 related pneumonia and as many as 80% of those who need intensive care – with mortality rates as high as 50%-80% for those who require mechanical ventilation. Currently, supportive care and interventions to assist breathing are the only treatments available for COVID-19 ARDS patients.
“What makes COVID-19 so dangerous is the way it attacks the lungs and induces such an intense inflammatory response that they are no longer able to transfer adequate oxygen to the blood,” says Dr. Duncan Stewart, CEO and Scientific Director of The Ottawa Hospital’s Research Institute and professor at the University of Ottawa. “MSCs have the ability to dampen inflammation to prevent it from becoming as severe, while at the same time bolstering other aspects of the immune response to remove pathogens and allow the organ to heal.”
Stewart and Dr. Lauralyn McIntyre, a critical care researcher at The Ottawa Hospital, confirmed the safety of MSCs for use in patients in a phase 1 trial completed in 2018 to treat septic shock, which can also lead to ARDS. This sepsis research was funded, in part, by Disease Team grants of over $2.2M from the Ontario Institute for Regenerative Medicine (OIRM) over the last five years.
The team will use those findings as a springboard to launch the CIRCA-19 (Cellular Immunotherapy for COVID-19-Related ARDS) trial, which is sponsored by The Ottawa Hospital’s Research Institute and funded via a $1.2 million grant from the Ontario COVID-19 Rapid Research Fund, with an additional $300,000 grant from the Stem Cell Network.
CIRCA-19 will enroll 27 patients with COVID-19 ARDS from intensive care units in Ottawa and other Ontario centres (including St. Michael’s Hospital in Toronto, with Drs. Claudia Dos Santos and Kim Connelly) in three rapid-fire phases over the next six months.
The safety phase will use bone-marrow derived MSCs Stewart’s team has banked in their Ottawa lab, and MSCs from the umbilical cord provided through a partnership the Center for Regenerative Therapies (CRTD) in Dresden, Germany will be used to assess the maximum feasible tolerated dose, as well as efficacy. MSCs culled from umbilical cord are similar to those derived from bone marrow but may have superior anti-inflammatory function, and are more readily available during a global pandemic, Stewart notes.
Stewart credits the thriving stem cell research and development ecosystem in Ontario for enabling the team to launch CIRCA-19 so quickly.
“The reason we are able shift gears to prioritize the study of MSCs for treating COVID-19 ARDS so rapidly is because of the investments in infrastructure we have made in the province in cell manufacturing capabilities that are critical for developing new technologies as well as expertise to design and manage clinical trials,” he says. “All of the necessary components were already in place so we could move rapidly.”
Photo credit: The Ottawa Hospital