One for treating diabetes The drug may provide new treatments for respiratory syncytial virus (RSV) bronchitis (inflammation and small airway obstruction in the lungs). A multidisciplinary team of the Vanderbilt research team demonstrated that liraglutide can alleviate the inflammatory response to RSV infection in a mouse model of disease.
The results of the study were published in the Journal of Allergy and Clinical Immunology.
Lilaglutide is one of six “GLP-1R agonists” approved for the treatment of type 2 diabetes. These drugs enhance insulin secretion in the pancreas by activating the glucagon-like peptide 1 receptor (GLP-1R).
“The link between GLP-1R signaling and lung inflammation is surprising,” said Dr. R. Stokes Peebles, MD, medical professor of Elizabeth and John Murray. His team is working on a doctor and colleague who studies diabetes and obesity, Kevin Niswender, MD, associate professor of medicine.
In the past few years, the two men have jointly guided their daughter’s basketball team.
“After a day of training, Kevin said, ‘you need to look at these drugs on your model,’” Peebles said.
Niswender explained that GLP-1R agonists have anti-inflammatory properties, but these drugs have not been tested in allergic types and virus-mediated airway inflammation studied by Pilbus and his team.
“We almost always try a new idea because you never know what might be successful,” Peebles said.
Infected mice with isolated RSV strains from infants who have been hospitalized for severe lower respiratory tract infections and bronchitis. The RSV strain induces high levels of inflammatory factors and airway mucus in mice, which mimic the severe infection of the patient.
Treatment of mice with liraglutide before or after RSV infection reduces inflammatory factor production in the lungs and reduces inflammation, airway responsiveness and airway mucus.
“This drug is a good way to reduce lung disease, suggesting that it may treat severe RSV infection,” Peebles said.
According to data from the National Institute of Allergy and Infectious Diseases, RSV bronchiolitis is the leading cause of hospitalization in US infants, with up to 125,000 children hospitalized each year. Adults over the age of 65 are also susceptible to lung disease with severe RSV infection.
Infants and children at high risk for RSV bronchiolitis can receive palivizumab to prevent RSV infection, but there is no treatment option after RSV infection.
“A large number of children without any risk factors develop RSV bronchiolitis and are hospitalized. They may be helpful like drugs like liraglutide,” Peebles said.
Niswender is working with Vanderbilt’s pharmaceutical chemists to develop more potent GLP-1R agonists that can be specifically targeted by lung inhalation.
Bloodworth also measured the antiviral immune response in mice infected with RSV and treated with liraglutide.
She found no difference in the mediators of antiviral immune responses, including interferon-gamma and certain white blood cells (Th1 T helper cells and natural killer cells).
“This is important because we don’t want to seek RSV treatment that has a negative impact on the viral immune response,” Bloodworth said.
Bloodworth also found that the first RSV infection treated with liraglutide did not block the protective immune response in the second RSV infection in mice.
To find a link between GLP-1R signaling and human RSV disease, the researchers conducted a full-phenotype association study (PheWAS) with Lisa, the chief data scientist at the Center for Precision Medicine. PheWAS looks for links between known genetic variations and phenotypes (such as diagnosis) in medical records.
With the existing database, the researchers discovered a genetic variant associated with a lower response to GLP-1. They then conducted an experiment for this variant in Vanderbilt’s biochemical library. They found that genetic variation is associated with acute bronchitis.
“We found a link between GLP-1R signaling and human bronchitis, a fact that confirms our research on mice, which is very exciting,” Bloodworth said.
Pebus said that these studies have opened up a whole new field of research.
“GLP-1 receptor is highly expressed in the lungs, but no one knows what it is doing,” he said. “We are studying the role of the endogenous GLP-1 receptor in the lungs – what happens if the receptor is missing, what happens when allergies and viral inflammation occur.”
Pebers And his colleagues are also investigating the use of GLP-1R agonists in obese and asthmatic patients.
He said: “There is an asthma epidemic among obese people. We are interested in these drugs and think it is a potential treatment for obesity and asthma.” (screw 209086)