Inhaled nebulized glatiramer acetate against Gram-negative bacteria is not associated with adverse pulmonary reactions in healthy, young adult female pigs

• Published in: PloS one 2019-10, Vol.14 (10), p.e0223647-e0223647
• Main Authors: Skovdal, Sandra M, Christiansen, Stig Hill, Johansen, Karen Singers, Viborg, Ole, Bruun, Niels Henrik, Jensen-Fangel, Søren, Holm, Ida Elisabeth, Vorup-Jensen, Thomas, Petersen, Eskild
• Format: Article
• Language: English
• Subjects: Administration, Inhalation; Animal welfare; Animals; Anti-infective agents; Antibacterial agents; Antibiotics; Antimicrobial activity; Antimicrobial agents; Antimicrobial peptides; Bacteria; Biochemistry; Biofilms; Biological membranes; Biology and Life Sciences; Bronchi - drug effects; Bronchi - microbiology; Bronchi - pathology; Bronchoconstriction; Bronchoconstriction - drug effects; Bronchopulmonary infection; Clinical medicine; Copolymer 1; Cystic fibrosis; Drug approval; EDTA; Engineering and Technology; Female; Food; Glatiramer acetate; Glatiramer Acetate - administration & dosage; Glatiramer Acetate - pharmacology; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Health aspects; Histochemistry; Histopathology; Hospitals; Immunology; Immunomodulation; Infection; Infectious diseases; Inflammation; Inhalation; Laboratories; Leukocyte Count; Lung - drug effects; Lung - microbiology; Lung - pathology; Lung diseases; Mannitol - administration & dosage; Mannitol - pharmacology; Medicine and Health Sciences; Membranes; Microbial drug resistance; Mucous Membrane - drug effects; Multidrug resistance; Multidrug resistant organisms; Multiple sclerosis; Nebulizers and Vaporizers; Oxygen; Peak pressure; Peptides; Pharmaceuticals; Physical Sciences; Physiological aspects; Pressure; Pseudomonas aeruginosa; Research and Analysis Methods; Respiration; Respiratory therapy; Respiratory tract; Respiratory tract diseases; Safety; Side effects; Swine; Women's health; Young adults; Youth
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0223647

The developmental speed of new antimicrobials does not meet the emergence of multidrug-resistant bacteria sufficiently. A potential shortcut is assessing the antimicrobial activity of already approved drugs. Intrudingly, the antibacterial action of glatiramer acetate (GA) has recently been discovered. GA is a well-known and safe immunomodulatory drug particular effective against Gram-negative bacteria, which disrupts biological membranes by resembling the activity of antimicrobial peptides. Thus, GA can potentially be included in treatment strategies used to combat infections caused by multidrug-resistant Gram-negatives. One potential application is chronic respiratory infections caused by Pseudomonas aeruginosa, however the safety of GA inhalation has never been assessed. Here, the safety of inhaling nebulized GA is evaluated in a preclinical pig model. The potential side effects, i.e., bronchoconstriction, respiratory tract symptoms and systemic- and local inflammation were assessed by ventilator monitoring, clinical observation, biochemistry, flowcytometry, and histopathology. No signs of bronchoconstriction assessed by increased airway peak pressure, Ppeak, or decreased oxygen pressure were observed. Also, there were no signs of local inflammation in the final histopathology examination of the pulmonary tissue. As we did not observe any potential pulmonary side effects of inhaled GA, our preliminary results suggest that GA inhalation is safe and potentially can be a part of the treatment strategy targeting chronic lung infections caused by multidrug-resistant Gram-negative bacteria.