Multimodal smart imaging of critical inflammatory processes in murine models of pulmonary fibrosis

Lead Research Organisation: University of Edinburgh
Department Name: MRC Centre for Inflammation Research

Abstract

Model systems that exist today may not accurately reflect what is actually going on in human disease. One crucial problem is that we have been unable to visualise molecular events within animal models and humans until cutting edge technology has been launched. We wish to improve the treatment of a condition called idiopathic pulmonary (lung) fibrosis. This condition has a worse mortality than most cancers and there are currently no effective drug treatments. The fibrotic (scarring) process in pulmonary fibrosis is similar to that in other parts of the body such as liver and kidney. This research will apply cutting edge imaging to discover what key mechanisms are being switched on and off at different stages of the disease process. Extrapolating this to human disease is of utmost importance and will lead to new targeted therapies for inflammatory/scarring conditions of the lung and other organs.

Technical Summary

Idiopathic Pulmonary fibrosis (IPF) is a devastating inflammatory/scarring disease of the lungs. It is associated with a median survival of 3 years, and no current drug interventions have shown any clinical benefit. Part of the problem in new drug development for this and other inflammatory/scarring diseases of the lungs, and other organs, is the relatively slow progress of the disease and the lack of good, meaningful biomarkers. Thus there is a pressing need for improved animal models of these diseases in order to better understand the links between inflammation and tissue destruction/scarring, develop incisive biomarkers that can readily be translated into humans and more rapidly generate, and assess, novel mechanism-based drug treatments. A fundamental problem with existing animal models is that none of the underlying pathogenic processes have been properly validated in situ. We propose to address this by applying cutting-edge mutimodality optical and positron emission tomographic imaging to established models of murine pulmonary fibrosis in a fashion which will validate PET and other imaging techniques for application in human disease and then evaluate interventions that may be of clinical benefit.

Publications

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Dhaliwal K (2012) Monocytes control second-phase neutrophil emigration in established lipopolysaccharide-induced murine lung injury. in American journal of respiratory and critical care medicine

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Mills B (2021) Molecular detection of Gram-positive bacteria in the human lung through an optical fiber-based endoscope. in European journal of nuclear medicine and molecular imaging

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Svensen N (2011) Screening of a combinatorial homing peptide library for selective cellular delivery. in Angewandte Chemie (International ed. in English)

 
Description DPFS Scheme-Molecular Imaging of key Targets in the Fibrogenic Pathway in Man
Amount £971,797 (GBP)
Funding ID MR/J014702/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2012 
End 08/2015
 
Description Developmental Clinical Studies-validation of the utility of a novel smartprobe detecting neutrophils
Amount £2,357,633 (GBP)
Funding ID MR/J010901/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 07/2013 
End 07/2016
 
Description Health Innovation Challenge Funding
Amount £1,205,232 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 07/2011 
End 07/2015
 
Description MRC Developmental Pathway Funding Scheme (DPFS)
Amount £600,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 08/2009 
End 08/2011
 
Title improved murine models of human lung disease 
Description improved murine models of human lung disease for the purpose of molecular optical imaging translational research 
Type Of Material Model of mechanisms or symptoms - mammalian in vivo 
Year Produced 2012 
Provided To Others? No  
Impact in development