We propose Colony Stimulating Factor 1 (CSF-1) as an effective therapy for the treatment of ARDS, the leading cause of respiratory failure in ICU patients who require mechanical ventilation.
ARDS is a disease characterised by dysfunctional neutrophilic inflammation. We propose to use CSF-1 to expand lung monocyte derived interstitial macrophage populations to promote neutrophil clearance from the lungs and promote inflammation resolution. ARDS has a high mortality rate (around 45%) and survivors often suffer long term problems. Therefore there is a significant unmet need for effective pharmacotherapies that can reduce ARDS mortality.
Treatment of lung disease associated with dysfunctional neutrophilic inflammation by:
Acute respiratory distress syndrome (ARDS) is a life-threatening condition for which no effective therapies currently exist. ARDS is the leading cause of respiratory failure in ICU patients who require mechanical ventilation. ARDS has a high mortality rate (around 45%) and survivors often suffer long term problems. Most recently, the SARS-CoV-2 pandemic has resulted in large numbers of patients presenting with COVID-19 induced ARDS. As a consequence, there is a significant unmet need and, thus, commercial opportunity, for effective pharmacotherapies that can reduce ARDS mortality.
ARDS is caused by an acute inflammatory response in the lungs which leads to hypoxia. It is believed that hypoxic conditions alter the function and survival of neutrophils resulting in a hyperinflammatory response that is damaging.
Edinburgh researchers have shown that it is possible to use CSF-1 to increase mononuclear cell number, and/or induce a pro-restorative phenotype in mononuclear cells for use in the treatment of lung disease such as ARDS.
Publication WO2020234568A1 - TREATMENT OF ARDS
Mirchandani AS, Jenkins SJ, Bain CC, Sanchez-Garcia, MA, Lawson H, Coelho P, Murphy F, Griffith D, Zhang A, Morrison T, Ly T, Arienti S, Sadiku P, Watts ER, Dickinson RS, Reyes L, Cooper G, Clark S, Lewis D, Kelly V, Spanos C, Musgrave KM, Delaney L, Harper I, Scott J, Parkinson NJ, Rostron AJ, Baillie KJ, Clohisey S, Pridans C, Campana L, Starkey-Lewis, Simpson J, Dockrell D, Schwarze J, Hirani N, Ratcliffe PJ, Pugh CWP, Kranc K, Forbes S, Whyte MKB, Walmsley SR. Hypoxia shapes the immune landscape in lung injury promoting inflammation persistence. Nat. Immunol. 2022; 23:927-939.
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