Could salmon and other fatty fish unlock new treatments for severe lung disease?

BUFFALO, N.Y. —  Lung inflammation and injury can quickly turn into acute respiratory distress syndrome (ARDS) in patients with pneumonia, COVID-19 and other conditions.

ARDS affects more than 200,000 people annually in the United States. Of those, 30 to 50%, according to Zhenjia Wang, PhD, SUNY Empire Innovation Professor in the School of Pharmacy and Pharmaceutical Sciences at the University at Buffalo. He recently joined UB and is conducting research on nanomedicine.

“Besides ventilation and draining fluid from the lungs, the only therapies currently used for this condition are anti-inflammatory drugs like steroids to blunt the inflammation, Wang notes. “These aren’t always successful and make patients more susceptible to secondary infections.”

Wang recently received a $2 million, four-year grant from the National Heart, Lung and Blood Institute (NHLBI) of the National Institutes of Health to look for a safer and more effective treatment using omega-3 fatty acids.

He is collaborating with Elsa Bou Ghanem, PhD, associate professor in the Department of Microbiology and Immunology in the Jacobs School of Medicine and Biomedical Sciences at UB.

“Acute lung inflammation/injury (ALI) is a dysregulated inflammation disease, and it quickly precipitates to the more severe ARDS,” Wang says. “In the United States alone, the mortality rate is unacceptably high. ARDS also represents a major economic burden for health care systems.”

Bou Ghanem, who has expertise in immunology and neutrophils (one type of white blood cells), says, “Neutrophils play a central role in ARDS, and targeting neutrophils using nanotechnology could impact the development of new therapeutics.”

First, Wang and Bou Ghanem want to see if the body can stop the inflammatory process ­on its own — using molecules found within the omega-3 fatty acids most of us know is found in salmon and other fatty fish.

“A lot of people take omega-3 supplements to help prevent vascular diseases because omega-3 fatty acids are effective at combatting inflammation,” Wang says. “Recent studies show that the body converts one type of omega-3 fatty acid, DHA (docosahexaenoic acid), into healing molecules called resolvins. They are called this because they can resolve the inflammation, encourage healing and allow the immune system to keep fighting infections.”

While resolvins RvD1 and RvD2 show potential for calming inflammation in laboratory studies, it has proven difficult to manufacture a drug using these compounds due to stability issues, Bou Ghanem notes.

Wang’s hypothesis is to deliver DHA into neutrophils that then stick to the blood vessels in the lungs using fat-based particles called liposomes. The specific LOX5/15 enzyme then converts DHA into the resolvins. This process, in effect, makes resolvins in the inflamed lungs.

To test this, the researchers will use mice with acute lung injury models and give them nanoparticles with the hope of healing the injuries.

They have three main goals. The first is to develop the best liposomes for delivering DHA directly to neutrophils. The second is to determine whether those neutrophils actually produce more resolvins after receiving DHA, and the third is to see whether this treatment improves ARDS in the animal studies.

If this strategy works, it could represent a completely new way of treating inflammatory diseases and conditions beyond ARDS, including some autoimmune diseases, arthritis, and Crohn’s disease, Wang says, adding that in all diseases and conditions associated with inflammation, neutrophils play a central role.

“If we can target the neutrophil using our nanoparticles, we can treat most inflammatory disease,” he says. “The success of this application would be a paradigm shift.”