The Sathyamoorthy family heard on the news that COVID-19 had reached Aspen, Colorado, just as they were leaving the city. It was March 2020, and the family’s road trip would come to an end with a long, worried drive — and the birth of an idea.
Before Dr. Mohanakrishnan Sathyamoorthy, a cardiologist and scientist in Fort Worth, arrived home, he’d already started thinking about cytokine storms, the body’s overzealous and, sometimes, life-threatening response to an infection. He’d read people with COVID-19 were experiencing these storms, which could in turn lead to the failure of multiple organs. He wondered, then, if a drug that calmed the body’s immune response could prevent the storms from happening.
After his rounds the next day, he sat down and started drafting. His proposal would require further research, and the research required a team. He gathered a cohort of physicians across disciplines in North Texas to form the Fort Worth Clinical Sciences Working Group, a volunteer research team trying to determine if an already-existing drug could treat the sickest COVID-19 patients.
A year and six months later, after about 40 Zoom meetings and five in-depth proposal revisions, the group’s efforts came to fruition. In late September, the U.S. Food and Drug Administration approved the group’s research for clinical trials. And though the journey will stretch longer still — the group needs local hospitals’ institutional review boards to approve its research, hundreds of thousands of dollars’ worth of funding and, ultimately, for the trials to help patients heal — the September milestone is a victory for innovation and Fort Worth, Sathyamoorthy said.
He thinks “it’s the first time (in the city’s history) a working group of clinician scientists has come together to arrive at this endpoint.”
Though the FDA approval was new, the collaboration across disciplines and hospital systems was not. The physicians in the research group had worked together before — both in research and in taking care of patients, according to Dr. Stevan Gonzalez, a local physician and research group member. For example, Gonzalez and Sathyamoorthy both teach at the TCU and UNTHSC School of Medicine and have partnered in treating hundreds of patients with both liver and heart problems.
All involved brought their own expertise to the group. For Gonzalez, the senior co-investigator for the research, that expertise is transplant medicine.
“You wouldn’t think that transplant medicine would have any application toward things like the COVID-19 infection,” he said. “But actually, transplant medicine involves a great deal of immunology.”
When a person receives a liver transplant, for example, the immune system may reject the new organ, which can lead to organ failure. It’s common practice to give transplant patients medicine that targets the body’s immune response and, ideally, prevents rejection, Gonzalez said.
“The medication that we developed the study for is commonly used in a transplant setting,” he said, “because it targets a specific part of the immune system that is involved in transplant rejection — but can also be involved in the triggering of the immune system in something like a cytokine storm.”
The drug, basiliximab, is a monoclonal antibody that helps slow down the body’s immune response and, in a transplant setting, keep someone’s body from rejecting a new kidney. The FDA approved basiliximab as a treatment for kidney transplant patients in 1998.
Slowing the body’s immune response with basiliximab may also keep people hospitalized with COVID-19 from developing a cytokine storm — at least, that’s the hypothesis, Sathyamoorthy said.
When a person gets sick, the immune system releases proteins called cytokines into the body to combat the infection. A cytokine storm occurs if the body releases too many cytokines, some of which increase inflammation, too soon.
The body becomes severely inflamed, destroying tissue and causing organs to fail. “Think of it almost like setting everything on fire,” he said.
In the early months of the pandemic, treating COVID-19 patients experiencing a cytokine storm, many of whom were awake and struggling to breathe, was especially “harrowing,” he said: “That’s what was so tragic in the first few months of this.”
“It was really a challenge, not just in the United States but throughout the world, and why the mortality rates were so high,” he said, “because it took the clinical community time to realize that this out-of-control inflammatory storm was the upstream driver of all of the challenges we were seeing in the hospital.”
As the pandemic stretched on, physicians used various tools, like steroids and other monoclonal antibodies, to manage the cytokine storm. The latter treatment may only be helpful in very specific patient populations, Sathyamoorthy said. He’s hopeful basiliximab will have a “more substantial impact” for all kinds of people.
“We hope to improve the standard of care,” he said.
The group’s next step is to secure approval from institutional review boards, which monitor the welfare of human research subjects, within Baylor Scott & White All Saints Medical Center Fort Worth, John Peter Smith Hospital and Texas Health Harris Methodist Hospital Fort Worth and enlist eligible COVID-19 patients to join the trials. If a person hospitalized with COVID-19 wants to participate in the study, they can ask their physician, who should be able to connect the patient to the research team to see if they’re eligible, Sathyamoorthy said.
Clinical trials involve multiple phases. If the drug proves safe and effective for treatment against COVID-19, the trials will expand to include more people. The process can take years and be costly. Sathyamoorthy estimates the research group still needs a few hundred thousand dollars to purchase the basiliximab and hire staff to carry out the trials.
What they’ve already accomplished is a boon for the city, according to Kathleen Otto, the chief executive officer for BioNorthTexas, an organization that promotes collaboration within the biotech community in North Texas.
Projects like this one contribute to Fort Worth’s “reputation of great science” and “mindset of innovation,” which can take courage, she said.
“A lot of innovation fails. A lot of things fail,” she said. “In science, that’s how you get to success — by having failures.”
As a city brimming with medical and public health institutions, as well as a diverse population, Fort Worth creates space for clinical trials like these to be successful, she said: “Fort Worth is a gold mine. There’s a lot of good science in Fort Worth.”
“Fort Worth is a gold mine. There’s a lot of good science in Fort Worth.”– Kathleen Otto, CEO of BioNorthTexas
“There’s no better answer to the future of Fort Worth than scientific innovation and health care innovation,” she said.
For Sathyamoorthy, the victory lies, in part, with the commitment of a motley group of physician volunteers. The FDA approval process is robust — it meets and even exceeds “big-time scientific peer review,” he said. Also, it’s typically pursued by major academic centers or large-budget pharmaceutical companies, not “voluntary folks in a working group setting.”
“Can you imagine how many hours we spent doing five full-set revisions, to get to the point where the FDA was like, ‘This is a great study, it needs to take place, we feel like you’ve met all the regulatory hurdles necessary for us to approve this for a human subjects study’?” he said.
He hopes the group can serve as a model for collaboration among other thought leaders in Fort Worth: “We want this to serve as an example of what’s possible when like-minded people come together, set a goal and are absolutely tireless in accomplishing it.”
Alexis Allison is the health reporter at the Fort Worth Report. Her position is supported by a grant from Texas Health Resources. Contact her by email or via Twitter. At the Fort Worth Report, news decisions are made independently of our board members and financial supporters. Read more about our editorial independence policy here.