Health & Environmental Research Online (HERO)


Print Feedback Export to File
2623341 
Journal Article 
Abstract 
Inhaled cationic airway lining modulator (iCALM) therapy, a novel aerosol treatment for respiratory infections reduces clinical symptoms and transmission of Influenza A infection 
Hava, DL; Griel, LC; Dehaan, WH; Hubeau, C; Kenyon, J; Lipp, MM; Lambkin-Williams, R; Balasingam, S; Clarke, RW 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A6846 
English 
WOS:000208771005442 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
RATIONALE: Morbidity associated with influenza illness has significant worldwide impact. Pathogen-targeted anti-viral therapies are hampered by resistance and adverse event profiles. Pulmatrix is developing a safe, host-targeted aerosol therapy that takes advantage of the inherent biophysical and host defense properties of the airway to treat and prevent influenza clinical symptoms and reduce airborne contagion.

METHODS: iCALM efficacy was evaluated in ferret and swine models of influenza. Ferret Influenza model (prophylaxis) Ferrets (1200-2000g) were treated with iCALM or control by nose-only inhalation 1 hr pre-infection followed by BID dosing for 7 days post-infection (PI; ~0.58 mg/kg/dose). Ferrets were intranasally infected (H3N2); clinical symptoms including peak body temperatures were assessed. Swine influenza model (treatment and contagion) Piglets (6-8 weeks old) were infected intranasally (H1N1) and were treated once daily with nebulized iCALM aerosol on day 2 and day 3 PI (~0.57 mg/kg/dose). Clinical symptoms of infection, including body temperatures were observed PI and pathology was scored as the percentage of lung consolidation (%LC). For contagion studies, on day 2 and 3 PI, infectious swine were treated once daily with nebulized iCALM aerosol (~0.57 mg/kg/dose) or control. Immediately following aerosol treatment, naïve swine (n=8 total, 4/group) were exposed to the combined exhaled breath of the iCALM-treated or untreated animals for 1h. Naïve swine were observed for clinical symptoms and %LC.

RESULTS: iCALM treated ferrets exhibited significantly reduced peak body temperatures, weight loss, and nasal wash inflammatory cell counts compared to control (p<0.05). iCALM-treated swine exhibited significantly reduced body temperatures and had reduced %LC. In untreated animals, %LC scores of 25% or higher were common (n=5/8) and all animals had some %LC (n=8/8; Mean consolidation=47±11%). In contrast, in the treated animals, the %LC scores ranged between zero and 10%, with half of the animals showing no lung pathology (n=4/8; Mean consolidation=4±1%). Naïve swine exposed to the exhaled breath of infected, untreated swine all developed fever (mean increase of 1.9 °C) and lung consolidation (10-25%). In contrast, naïve animals exposed to the exhaled breath of infected, iCALM-treated animals did not develop fever and showed no %LC suggesting reduced transmission of infection.

CONCLUSIONS: The results of these studies suggest that iCALM is a novel therapeutic approach for influenza that may provide a therapeutic benefit to primary infections as well as beneficially impact infection control. Additional research is ongoing to understand the dual mechanistic action of the therapy in terms of reducing clinical symptoms and preventing transmission. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010