JUPITER, Fla. — Doctors have few options for patients who develop a life-threatening lung condition called acute respiratory distress syndrome, or ARDS.
A frequent cause of death during the COVID-19 pandemic, ARDS occurs when an inflammatory cascade triggered by infection or injury leaks fluid into the lungs, crashing blood oxygen levels. Nearly 40% of people affected die.
A proof-of-concept study led by a scientist at the University of Florida suggests a monoclonal antibody that targets a master regulator of inflammation, called NAMPT, could offer much-needed treatment for ARDS.
Monoclonal antibodies are manufactured proteins based on natural immune factors that seek out and engage specific biological targets. Since the 1990s, doctors have increasingly prescribed monoclonal antibody therapies for many diseases, including cancer, Crohn's disease and rheumatoid arthritis.
In the study, a monoclonal antibody treatment called ALT-100 was used in an early phase clinical trial that enrolled 15 patients at academic medical centers in six cities across the United States, including UF Health Shands Hospital in Gainesville.
Participants diagnosed with ARDS were randomly selected to receive either a saline solution placebo or ALT-100.
Over the next 28 days, the ALT-100 group experienced significantly greater ventilator-free days – 21 on average versus 14. They also showed reduced inflammatory markers and lower organ failure scores, according to the report published last week in the American Journal of Respiratory and Critical Care Medicine .
Of key importance, the study showed that the ALT-100 treatment's safety profile appeared to be comparable to that of people given a placebo, said Joe G.N. Garcia , M.D., the study's first author and the physician-scientist who developed ALT-100.
Garcia is associate vice president for research at UF Health and director of The Center for Inflammation Science and Systems Medicine at The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology .
An estimated 500,000 people a year are diagnosed with ARDS every year in the United States. Globally, 2 million people are affected.
"There are no FDA-approved therapies to give these patients, and given the unacceptable mortality and pervasiveness of the disease, ARDS treatment remains one of the greatest unmet needs in medicine," Garcia said.
Garcia traces the development of the ALT-100 treatment to his time in the late 1990s as chief of pulmonary and critical care medicine at Johns Hopkins University, where he also served as an ICU physician.
Frustrated at the lack of good treatment options for ARDS patients, he set out to find one. He began by studying which genes were active in the sick patients. That led to the discovery of a new player in the inflammatory response, called NAMPT. In patients who had mutations that impaired the breakdown of NAMPT, his lab showed that unremitting inflammation, referred to as a "cytokine storm" could develop, leading to organ failure and death.
His lab's work eventually led to the development of the ALT-100 monoclonal antibody, which directly targets extracellular NAMPT. Since then, Garcia's research groups have studied the antibody's ability to prevent and treat illness in models of some 20 conditions, including liver fibrosis, pregnancy loss, advanced prostate cancer, heart disease, neonatal necrotizing enterocolitis, lupus-related vasculitis and more.
"This is a Humira-like drug, targeting the innate immune response, which is why it has profound implications for diseases like cancer, organ fibrosis and so on," he said.
But unlike similar medications, ALT-100 does not dampen the body's ability to fight infection, it simply puts the brakes on an excessive immune response. An important limitation of the study is the small number of participants, Garcia said. The group had hoped to enroll 60 patients, but their strict inclusion criteria required that a patient be treated within six hours of diagnosis, causing delays, and they would have needed additional funding to add additional participants, Garcia said.
"Even though we were only able to enroll 15 patients, the data we are getting is simply incredible," Garcia said. "Particularly the ARDS data showing that the monoclonal antibody improved both ventilator-free days and organ failure scores, because organ failure is the main cause of ARDS-related mortality."
Looking ahead, he hopes to obtain funding for a larger clinical trial. Beyond receiving U.S. Food and Drug Administration approval to conduct ARDS trials, Garcia has the green light to study ALT-100 in patients with progressive pulmonary fibrosis, a buildup of scar tissue in the lungs often seen in autoimmune disease, acommon in ARDS survivors.
