The long term aims of the study are to characterize and develop next generation aerosol formulations for the treatment and anti-contagion of a wide range of respiratory infectious diseases, that are more efficacious and user friendly than current formulations. Specifically we aim to identify a lead therapeutic for the treatment and anti-contagion of Influenza (NIAID Category C Priority Pathogen). Background Respiratory infections are a significant source of morbidity and mortality in the developed and developing world. Conventional approaches to preventing or treating infections are limited by pathogen specificity ("one bug one drug") and emerging resistance, which collectively hinder their deployment and utility. Pulmatrix is developing a novel aerosol therapy, containing simple cations (e.g., calcium), that may provide a broad spectrum, mass use approach for the treatment of a wide range of viral and bacterial respiratory infections. The principle of this approach is based on modulation of the surface rheological properties of the airway lining fluid (ALF) of the respiratory epithelium and stimulation of the innate and adaptive immunological responses to both viral and bacterial pathogens, by cationic aerosols. These novel aerosols have been shown to: reduce exhaled bioaerosols in humans;arrest transmission of and treat porcine influenza;treat murine bacterial pneumonia;and alter the rheological properties of mucus mimetics, suggesting that additional aerosol therapies may be developed to treat and contain both bacterial and viral respiratory infections which, in turn, may lead to a broad spectrum treatment for respiratory infections Hypothesis Treatment and anti-contagion effects of salt aerosols occur by alteration of the rheological properties of the ALF leading to reduced bioaerosol production from the ALF and/or by altering the course of infection.
Specific Aims 1. Define the effect of salt aerosols on rheology and the formation of bioaerosols from airway lining fluid using an in vitro simulated cough system and interfacial stress rheometry;2. Examine the effect of salt aerosols on pathogen infectivity by testing the ability of bacteria and viruses to cross mucus mimetics that have been exposed to salt aerosols and whether salt aerosols reduce the infectivity of Influenza A in cell culture models;3. Determine, in vivo, the effect of decreased bioaerosol production on airborne transmission and respiratory infection, in a porcine model of Influenza infection. Project Milestone: To identify a lead salt aerosol formulation for the treatment of influenza and for the suppression of exhaled bioaerosol production to be advanced into preclinical safety studies and additional preclinical models of infection.
Acute lower respiratory infections are a significant source of morbidity and mortality. These infections represent more than 6% of the total burden of disease worldwide, a higher burden than diseases such as HIV/AIDS, malaria, and diarrheal diseases. Therefore simple, broad spectrum, prophylactic/therapeutic strategies for combating these infections, such as salt aerosol formulations proposed herein are highly needed.